Rate Of Action Potential Discharge Research Articles

Kv2 channels contribute to neuronal activity within the vagal afferent-nTS reflex arc.

Diversity in the functional expression of ion channels contributes to the unique patterns of activity generated in visceral sensory A-type myelinated neurons versus C-type unmyelinated neurons in response to their natural stimuli. In the present study, Kv2 channels were identified as underlying a previously uncharacterized delayed rectifying potassium current expressed in both A- and C-type nodose ganglion neurons. Kv2.1 and 2.2 appear confined to the soma and initial segment of these sensory neurons; however, neither was identified in their central presynaptic terminals projecting onto relay neurons in the nucleus of the solitary tract (nTS). Kv2.1 and Kv2.2 were also not detected in the peripheral axons and sensory terminals in the aortic arch. Functionally, in nodose neuron somas, Kv2 currents exhibited frequency-dependent current inactivation and contributed to action potential repolarization in C-type neurons but not A-type neurons. Within the nTS, the block of Kv2 currents does not influence afferent presynaptic calcium influx or glutamate release in response to afferent activation, supporting our immunohistochemical observations. On the other hand, Kv2 channels contribute to membrane hyperpolarization and limit action potential discharge rate in second-order neurons. Together, these data demonstrate that Kv2 channels influence neuronal discharge within the vagal afferent-nTS circuit and indicate they may play a significant role in viscerosensory reflex function.NEW & NOTEWORTHY We demonstrate the expression and function of the voltage-gated delayed rectifier potassium channel Kv2 in vagal nodose neurons. Within sensory neurons, Kv2 channels limit the width of the broader C-type but not narrow A-type action potential. Within the nucleus of the solitary tract (nTS), the location of the vagal terminal field, Kv2 does not influence glutamate release. However, Kv2 limits the action potential discharge of nTS relay neurons. These data suggest a critical role for Kv2 in the vagal-nTS reflex arc.

Interactive effects of apneic and baroreflex stress on neural coding strategies in human muscle sympathetic nerve activity

The sympathetic nervous system exhibits patterns of action potential (AP) discharge in human muscle sympathetic nerve activity that suggest coding strategies express reflex specificity. This study explored the interactive effects of baroreceptor unloading using lower body negative pressure (LBNP) and volitional end-expiratory apnea (APN) on sympathetic postganglionic neuronal discharge patterns inferred from the firing patterns of differently sized sympathetic AP clusters. Seven individuals were studied using multiunit microneurography (fibular) and a continuous wavelet approach to quantify AP discharge probability, recruitment, and latency during APN performed under ambient conditions, -10, and -40 mmHg LBNP. Compared with the ambient condition, LBNP increased AP discharge rate at -10 and -40 mmHg and recruited larger previously silent sympathetic neurons at -40 mmHg. Compared with spontaneous breathing, APN increased AP discharge when performed during the ambient condition (Δ351 ± 132 AP/min), -10 mmHg (Δ423 ± 184 AP/min), and -40 mmHg (Δ355 ± 278 AP/min; main effect APN: P < 0.01; LBNP-by-APN interaction: P = 0.55). APN recruited larger previously silent AP clusters during the ambient condition (Δ4 ± 3; P < 0.02) and -10 mmHg (Δ4 ± 3; P < 0.01), but not -40 mmHg (Δ0 ± 2; P = 0.53; LBNP-by-APN: P < 0.01). LBNP did not affect AP latency. However, APN reduced AP latency similarly during all conditions (ambient pressure: Δ-0.04 ± 0.04s, -10 mmHg: Δ-0.03 ± 0.03s, -40 mmHg: Δ-0.03 ± 0.04s; main effect APN: P < 0.01; LBNP-by-APN: P = 0.48). These data indicate that apneic and baroreflex mechanisms appear to additively modify the axonal discharge rate of previously active sympathetic postganglionic neurons and interact to affect recruitment of previously silent sympathetic neurons. Reductions in AP latency due to apneic stress were not impacted by baroreflex unloading.NEW & NOTEWORTHY Discrete physiological stressors differentially affect sympathetic postganglionic neuronal rate-, population-, and temporal-coding strategies. When performing end-expiratory apnea (APN) during graded baroreflex unloading via lower body negative pressure (LBNP), we found: 1) augmented sympathetic axonal firing probability, 2) recruitment of larger and previously silent sympathetic postganglionic neurons at ambient and -10 mmHg, but not -40 mmHg LBNP, and 3) APN reduced axonal discharge latency similarly across all conditions, independent of the level of baroreflex unloading.

Sympathetic Discharge Patterns and Neurovascular Transduction Following Acute Intermittent Hypoxia

BackgroundMuscle sympathetic nerve activity (MSNA) is augmented in patients with sleep apnea. This increase in activity is due to increases in firing probability and mean firing rates of individual vasoconstrictor neurons, in addition to multiple within‐burst firing; however, contributing mechanisms and the impact of such firing patterns on peripheral vascular tone are less clear. We examined the effect of acute intermittent hypoxia (IH) on sympathetic neural firing and recruitment strategies and the relationship between changes in MSNA and neurovascular transduction following acute IH. We hypothesized exposure to acute IH would increase MSNA via an increase in action potential (AP) discharge rates and within‐burst firing. We further hypothesized any change in discharge patterns following acute IH would be positively related to a change in neurovascular transduction.MethodsBlood pressure (brachial arterial catheter) and MSNA (microneurography of the peroneal nerve) were assessed in 17 healthy adults (11M/6F; 31 ± 1 yrs) during quiet normoxic rest prior to and following 30‐min of experimental IH [30‐s hypoxic (0.05 FiO2) exposures alternating with 90‐s room air breathing]. AP patterns were studied from the filtered raw MSNA signal using wavelet‐based methodology. The slope of the relationship between diastolic blood pressure (DBP) and the preceding MSNA burst area at a fixed cardiac cycle lag was used to quantify neurovascular transduction.ResultsIH resulted in 15 events where oxygen saturation was reduced (SpO2: 99 ± 1% vs 92 ± 1%, P&lt;0.01). Compared to baseline, multi‐unit MSNA burst incidence (33 ± 4 to 43 ± 5 bursts/100 heart beats), AP incidence (272 ± 50 to 501 ± 112 AP/100 heart beats) and AP content per integrated burst (7 ± 1 to 10 ± 1 AP/burst; 4 ± 1 to 5 ± 1 clusters/burst) were increased following IH (all P&lt;0.05). Neurovascular transduction was not altered following IH (P=0.34); however, there was a positive relationship between the change (Δ) in neurovascular transduction (mmHg/%/s) and changes in AP discharge rate (AP/100 heart beats; R=0.52, P=0.03) and within‐burst firing (AP/burst; R=0.38, P=0.14) following IH.ConclusionsAcute IH increases sympathetic neuronal discharge by increasing within‐burst firing of low‐threshold axons. A positive relationship exists between increases in the neural discharge rates and neurovascular transduction following acute IH, such that those individuals with the greatest increase in AP firing exhibited the greatest increase in transduction of sympathetic activity into blood pressure. These data may have important implications for mechanistic understanding of sympathetic activation in sleep apnea and its down‐stream effects, including the development of hypertension and cardiovascular disease.Support or Funding InformationFunding: NIH HL130339, Mayo Clinic Center for Biomedical Discovery, Mizzou HES PURE, APS UGSRF.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impaired Nociception in the Diabetic Ins2+/Akita Mouse.

The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the Ins2+/Akita mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical and thermal nociception and a significant loss of intraepidermal nerve fibers. Electrophysiological investigations of skin-nerve preparations identified a reduced rate of action potential discharge in Ins2+/Akita mechanonociceptors compared with wild-type littermates, whereas the function of low-threshold A-fibers was essentially intact. Studies of isolated sensory neurons demonstrated a markedly reduced heat responsiveness in Ins2+/Akita dorsal root ganglion (DRG) neurons, but a mostly unchanged function of cold-sensitive neurons. Restoration of normal glucose control by islet transplantation produced a rapid recovery of nociception, which occurred before normoglycemia had been achieved. Islet transplantation also restored Ins2+/Akita intraepidermal nerve fiber density to the same level as wild-type mice, indicating that restored insulin production can reverse both sensory and anatomical abnormalities of diabetic neuropathy in mice. The reduced rate of action potential discharge in nociceptive fibers and the impaired heat responsiveness of Ins2+/Akita DRG neurons suggest that ionic sensory transduction and transmission mechanisms are modified by diabetes.

The aging neuromuscular system and motor performance.

Age-related changes in the basic functional unit of the neuromuscular system, the motor unit, and its neural inputs have a profound effect on motor function, especially among the expanding number of old (older than ∼60 yr) and very old (older than ∼80 yr) adults. This review presents evidence that age-related changes in motor unit morphology and properties lead to impaired motor performance that includes 1) reduced maximal strength and power, slower contractile velocity, and increased fatigability; and 2) increased variability during and between motor tasks, including decreased force steadiness and increased variability of contraction velocity and torque over repeat contractions. The age-related increase in variability of motor performance with aging appears to involve reduced and more variable synaptic inputs that drive motor neuron activation, fewer and larger motor units, less stable neuromuscular junctions, lower and more variable motor unit action potential discharge rates, and smaller and slower skeletal muscle fibers that coexpress different myosin heavy chain isoforms in the muscle of older adults. Physical activity may modify motor unit properties and function in old men and women, although the effects on variability of motor performance are largely unknown. Many studies are of cross-sectional design, so there is a tremendous opportunity to perform high-impact and longitudinal studies along the continuum of aging that determine 1) the influence and cause of the increased variability with aging on functional performance tasks, and 2) whether lifestyle factors such as physical exercise can minimize this age-related variability in motor performance in the rapidly expanding numbers of very old adults.

Self-regulation of adult thalamocortical neurons.

The thalamus acts as a conduit for sensory and other information traveling to the cortex. In response to continuous sensory stimulation in vivo, the firing rate of thalamocortical neurons initially increases, but then within a minute firing rate decreases and T-type Ca(2+) channel-dependent action potential burst firing emerges. While neuromodulatory systems could play a role in this inhibitory response, we instead report a novel and cell-autonomous inhibitory mechanism intrinsic to the thalamic relay neuron. Direct intracellular stimulation of thalamocortical neuron firing initially triggered a continuous and high rate of action potential discharge, but within a minute membrane potential (Vm) was hyperpolarized and firing rate to the same stimulus was decreased. This self-inhibition was observed across a wide variety of thalamic nuclei, and in a subset firing mode switched from tonic to bursting. The self-inhibition resisted blockers of intracellular Ca(2+) signaling, Na(+)-K(+)-ATPases, and G protein-regulated inward rectifier (GIRK) channels as implicated in other neuron subtypes, but instead was in part inhibited by an ATP-sensitive K(+) channel blocker. The results identify a new homeostatic mechanism within the thalamus capable of gating excitatory signals at the single-cell level.

Functional impact of the hyperpolarization‐activated current on the excitability of myelinated A‐type vagal afferent neurons in the rat

1. The hyperpolarization-induced, cation-selective current I(h) is widely observed in peripheral sensory neurons of the vagal and dorsal root ganglia, but the peak magnitude and voltage- and time-dependent properties of this current vary widely across afferent fibre type. 2. Using patch clamp investigations of rat isolated vagal ganglion neurons (VGN) identified as myelinated A-type afferents, we established a compendium of functional correlates between changes in membrane potential and the dynamic discharge properties of these sensory neurons as a result of the controlled recruitment of I(h) using the current clamp technique. 3. Two robust responses were observed in response to hyperpolarizing step currents: (i) upon initiation of the negative step current, there was a rapid hyperpolarization of membrane potential followed by a depolarizing voltage sag (DVS) towards a plateau in membrane potential as a result of steady state recruitment of I(h); and (ii) upon termination of the negative step current, there was a rapid return to the pretest resting membrane potential that often led to spontaneous action potential discharge. These data were strongly correlated (r(2) > 0.9) with a broad compendium of dynamic discharge characteristics in these A-type VGN. 4. In response to depolarizing step currents of increasing magnitude, the discharge frequency of the A-type VGN responded with increases in the rate of sustained repetitive discharge. Upon termination of the depolarizing step current, there was a post-excitatory membrane hyperpolarization of a magnitude that was strongly correlated with action potential discharge rate (r(2) > 0.9). 5. Application of the selective hyperpolarization-activated cyclic nucleotide gated (HCN) channel blockers ZD7288 (10 micromol/L) or CsCl (1.0 mmol/L) abolished I(h) and all of the aforementioned functional correlates. In addition to reducing the excitability of the A-type VGN to step depolarizing currents. 6. Because there is increasing evidence that the HCN channel current may represent a valid target for pharmacological intervention, the quantitative relationships described in the present study could potentially help guide the molecular and/or chemical modification of HCN channel gating properties to effect a particular outcome in VGN discharge properties, ideally well beyond merely selective blockade of a particular HCN channel subtype.

Bacterial cell products signal to mouse colonic nociceptive dorsal root ganglia neurons

This study examined whether bacterial cell products that might gain access to the intestinal interstitium could activate mouse colonic nociceptive dorsal root ganglion (DRG) neurons using molecular and electrophysiological recording techniques. Colonic projecting neurons were identified by using the retrograde tracer fast blue and Toll-like receptor (TLR) 1, 2, 3, 4, 5, 6, 9, adapter proteins Md-1 and Md-2, and MYD88 mRNA expression was observed in laser-captured fast blue-labeled neurons. Ultrapure LPS 1 microg/ml phosphorylated p65 NF-kappaB subunits increased transcript for TNF-alpha and IL-1beta and stimulated secretion of TNF-alpha from acutely dissociated DRG neurons. In current-clamp recordings from colonic DRG neurons, chronic incubation (24 h) of ultrapure LPS significantly increased neuronal excitability. In acute studies, 3-min superfusion of standard-grade LPS (3-30 microg/ml) reduced the rheobase by up to 40% and doubled action potential discharge rate. The LPS effects were not significantly different in TLR4 knockout mice compared with wild-type mice. In contrast to standard-grade LPS, acute application of ultrapure LPS did not increase neuronal excitability in whole cell recordings or afferent nerve recordings from colonic mesenteric nerves. However, acute application of bacterial lysate (Escherichia coli NLM28) increased action potential discharge over 60% compared with control medium. Moreover, lysate also activated afferent discharge from colonic mesenteric nerves, and this was significantly increased in chronic dextran sulfate sodium salt mice. These data demonstrate that bacterial cell products can directly activate colonic DRG neurons leading to production of inflammatory cytokines by neurons and increased excitability. Standard-grade LPS may also have actions independent of TLR signaling.

Brain‐derived neurotrophic factor drives the changes in excitatory synaptic transmission in the rat superficial dorsal horn that follow sciatic nerve injury

Peripheral nerve injury can promote neuropathic pain. The basis of the 'central sensitization' that underlies this often intractable condition was investigated using 14-20-day chronic constriction injury (CCI) of the sciatic nerve of 20-day-old rats followed by electrophysiological analysis of acutely isolated spinal cord slices. In addition, defined-medium organotypic spinal cord slice cultures were exposed for 5-6 days to brain-derived neurotrophic factor (BDNF, 200 ng ml(-1)) or to medium conditioned with activated microglia (aMCM). Since microglial activation is an early consequence of CCI, the latter manipulation allowed us to model the effect of peripheral nerve injury on the dorsal horn in vitro. Using whole-cell recording from superficial dorsal horn neurons, we found that both BDNF and CCI increased excitatory synaptic drive to putative excitatory 'radial delay' neurons and decreased synaptic excitation of inhibitory 'tonic islet/central' neurons. BDNF also attenuated synaptic excitation of putative GABAergic neurons identified by glutamic acid decarboxylase (GAD) immunoreactivity. Intrinsic neuronal properties (rheobase, input resistance and action potential discharge rates) were unaffected. Exposure of organotypic cultures to either BDNF or aMCM increased overall excitability of the dorsal horn, as seen by increased cytoplasmic Ca(2+) responses to 35 mm K(+) as monitored by confocal Fluo-4AM imaging. The effect of aMCM was attenuated by the recombinant BDNF binding protein TrkBd5 and the effect of BDNF persisted when GABAergic inhibition was blocked with SR95531. These findings suggest that CCI enhances excitatory synaptic drive to excitatory neurons but decreases that to inhibitory neurons. Both effects are mediated by nerve injury-induced release of BDNF from microglia.

Contribution of apamin-sensitive SK channels to the firing precision but not to the slow afterhyperpolarization and spike frequency adaptation in snail neurons

Apamin-sensitive small conductance Ca 2+-dependent K +(SK) channels are generally accepted as responsible for the medium afterhyperpolarization (mAHP) after single or train of action potentials. Here, we examined the functional involvement of these channels in the firing precision, post train AHP and spike frequency adaptation (SFA) in neurons of snail Caucasotachea atrolabiata. Apamin, a selective SK channel antagonist, reduced the duration of single-spike AHP and disrupted the spontaneous rhythmic activity. High frequency trains of evoked action potentials showed a time-dependent decrease in the action potential discharge rate (spike frequency adaptation) and followed by a prominent post stimulus inhibitory period (PSIP) as a marker of slow AHP (sAHP). Neither sAHP nor SFA was attenuated by apamin, suggesting that apamin-sensitive SK channels can strongly affect the rhythmicity, but are probably not involved in the SFA and sAHP. Nifedipine, antagonist of L-type Ca 2+ channels, decreased the firing frequency and neuronal rhythmicity. When PSIP was normalized to the background interspike interval, a suppressing effect of nifedipine on PSIP was also observed. Intracellular iontophoretic injection of BAPTA, a potent Ca 2+ chelator, dramatically suppressed PSIP that confirms the intracellular Ca 2+ dependence of the sAHP, but had no discernable effect on the SFA. During train-evoked activity a reduction in the action potential overshoot and maximum depolarization rate was also observed, along with a decrease in the firing frequency, while the action potential threshold increased, which indicated that Na + channels, rather than Ca 2+-dependent K + channels, are involved in the SFA.

Resonance of Spike Discharge Modulation in Neurons of the Guinea Pig Medial Vestibular Nucleus

The modulation of action potential discharge rates is an important aspect of neuronal information processing. In these experiments, we have attempted to determine how effectively spike discharge modulation reflects changes in the membrane potential in central vestibular neurons. We have measured how their spike discharge rate was modulated by various current inputs to obtain neuronal transfer functions. Differences in the modulation of spiking rates were observed between neurons with a single, prominent after hyperpolarization (AHP, type A neurons) and cells with more complex AHPs (type B neurons). The spike discharge modulation amplitudes increased with the frequency of the current stimulus, which was quantitatively described by a neuronal model that showed a resonance peak >10 Hz. Modeling of the resonance peak required two putative potassium conductances whose properties had to be markedly dependent on the level of the membrane potential. At low frequencies (< or =0.4 Hz), the gain or magnitude functions of type A and B discharge rates were similar relative to the current input. However, resting input resistances obtained from the ratio of the membrane potential and current were lower in type B compared with type A cells, presumably due to a higher level of active potassium conductances at rest. The lower input resistance of type B neurons was compensated by a twofold greater sensitivity of their firing rate to changes in membrane potential, which suggests that synaptic inputs on their dendritic processes would be more efficacious. This increased sensitivity is also reflected in a greater ability of type B neurons to synchronize with low-amplitude sinusoidal current inputs, and in addition, their responses to steep slope ramp stimulation are enhanced over the more linear behavior of type A neurons. This behavior suggests that the type B MVNn are moderately tuned active filters that promote high-frequency responses and that type A neurons are like low-pass filters that are well suited for the resting tonic activity of the vestibular system. However, the more sensitive and phasic type B neurons contribute to both low- and high-frequency control as well as signal detection and would amplify the contribution of both irregular and regular primary afferents at high frequencies.

Benzolamide, acetazolamide, and signal transduction in avian intrapulmonary chemoreceptors.

Intrapulmonary chemoreceptors (IPC) are CO(2)-sensitive sensory neurons that innervate the lungs of birds, help control the rate and depth of breathing, and require carbonic anhydrase (CA) for normal function. We tested whether the CA enzyme is located intracellularly or extracellularly in IPC by comparing the effect of a CA inhibitor that is membrane permeable (iv acetazolamide) with one that is relatively membrane impermeable (iv benzolamide). Single cell extracellular recordings were made from vagal filaments in 16 anesthetized, unidirectionally ventilated mallards (Anas platyrhynchos). Without CA inhibition, action potential discharge rate was inversely proportional to inspired PCO(2) (-9.0 +/- 0.8 s(-1). lnTorr(-1); means +/- SE, n = 16) and exhibited phasic responses to rapid PCO(2) changes. Benzolamide (25 mg/kg iv) raised the discharge rate but did not alter tonic IPC PCO(2) response (-9.8 +/- 1.6 s(-1). lnTorr(-1), n = 8), and it modestly attenuated phasic responses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduced tonic IPC PCO(2) response to -3.5 +/- 3.6 s(-1). lnTorr(-1) (n = 6), and severely attenuated phasic responses. Results were consistent with an intracellular site for CA that is less accessible to benzolamide. A model of IPC CO(2) transduction is proposed.

Postlesional epilepsy: the ultimate brain plasticity.

Lesions that occur either during fetal development or after postnatal brain trauma often result in seizures that are difficult to treat. We used two animal models to examine epileptogenic mechanisms associated with lesions that occur either during cortical development or in young adults. Results from these experiments suggest that there are three general ways that injury may induce hyperexcitability. Direct injury to cortical pyramidal neurons causes changes in membrane ion channels that make these cells more responsive to excitatory inputs, including increases in input resistance and a reduction in calcium-activated potassium conductances that regulate the rate of action potential discharge. The connectivity of cortical circuits is also altered after injury, as shown by axonal sprouting within pyramidal cell intracortical arbors. Enhanced excitatory connections may increase recurrent excitatory loops within the epileptogenic zone. Hyperinnervation attributable to reorganization of thalamocortical, callosal, and intracortical circuitry, and failure to prune immature connections, may be prominent when lesions affect the developing neocortex. Finally, focal injury can produce widespread changes in gamma-aminobutyric acid and glutamate receptors, particularly in the developing brain. All of these factors may contribute to epileptogenesis.

Chapter 2.1.1 Osmoregulation of vasopressin neurons: A synergy of intrinsic and synaptic processes

The release of vasopressin into the general circulation varies as a function of plasma osmolality and therefore plays a major role in systemic osmoregulation. In vivo, the secretion of this hormone in the neurohypophysis is primarily determined by the rate of action potential discharge of the magnocellular neurosecretory cells (MNCs) in the hypothalamus. Experiments done over the past 20 years have clarified much of the neurophysiological basis underlying this important osmoregulatory reflex. As discussed here, recent findings indicate that the regulation of the firing rate of MNCs during changes in systemic osmolality involves the concerted modulation of mechanosensitive ion channels in MNCs, as well as excitatory glutamatergic inputs derived from forebrain regions such as the organum vasculosum of the lamina terminalis.

PACAP27 and other neuropeptides in the inferior mesenteric ganglion.

The presence and location of PACAP27-like immunoreactivity (PACAP27-LI) in the colon-inferior mesenteric ganglion (IMG) reflex pathway and the effect of exogenously administered PACAP27 on the excitability of IMG are reported. The results provide morphological and electrophysiological support for the hypothesis that PACAP modulates reflex activity between the large intestine and IMG. The intense excitatory effect would be expected to increase the rate of action potential discharge in IMG neurons, increasing sympathetic drive to the colon thereby decreasing of colonic activity.

Ammonia attracts the haematophagous bug Triatoma infestans : behavioural and neurophysiological data on nymphs

1) Nymphs of the haematophagous bug Triatoma infestans (Heteroptera: Reduviidae) are attracted to volatiles from their own faeces on a servosphere. 2) Biological substrates attractive to triatomines release NH3: wetted triatomine faecal papers release NH3 at 256 ppb NH3 from a 60-g source and stale rabbit urine at 394 ppb from 200 ml. Ammonia released from aqueous NH3 also attracts bugs at doses of 3 ppb and 17 ppb on the servosphere. 3) Bugs typically show negative anemotaxis in a stimulus-free air-stream on the servosphere. At onset of stimulation with ammonia from either biological substrates or aqueous NH3 the bugs stop, move their antennae, turn and walk upwind, i.e. odour-mediated anemotaxis. 4) At lower NH3 doses a latency in attraction is recorded, but this latency disappears when the relative humidity of the stimulus delivery air-stream is dropped from 90 to 35%. 5) Electrophysiological recordings from single olfactory sensilla on antennae of Triatoma nymphs reveal two different types of NH3-excited receptors, both within grooved-peg sensilla. The responses of one of these receptor cells to NH3 has been studied in detail and shows that the action potential discharge rate is dose-dependent over the range 2–200 ppb. 6) The amplitudes of electroantennograms recorded from Triatoma nymphs to NH3 are dose dependent over the range 5–550 ppb.

Excitatory amino-acid receptors contribute to carotid sinus and vagus nerve evoked excitation of neurons in the nucleus of the tractus solitarius

To determine the role of excitatory amino-acid (EAA) receptors in afferent evoked excitation of neurons in the nucleus of the solitarius (NTS), responses of NTS neurons to activation of visceral afferent inputs were examined before and during iontophoretic application of the broad spectrum EAA receptor antagonist kynurenate (KYN). Iontophoretic application of KYN, at doses which attenuated glutamate but not substance P or acetylcholine evoked discharge, inhibited carotid sinus nerve (CSN) and vagus nerve evoked discharge. KYN attenuation of evoked responses was similar whether the evoked input was monosynaptic (CSN evoked discharge reduced by 50 ± 6% (mean ± SE; n = 5); vagus nerve evoked discharge reduced by 45 ± 4%, n = 6) or polysynaptic (CSN evoked discharge reduced by 48 ± 6%, n = 6; vagus nerve evoked discharge reduced by 45 ± 4%, n = 8). Spontaneous action potential discharge rate was reduced during KYN iontophoresis in 6 cells (1.8 ± 0.4 spikes/s vs. 0.7 ± 0.2 spikes/s). Iontophoretic application of a structural analogue of KYN which has no EAA receptor antagonist properties, xanthurenic acid, had no effect on glutamate, CSN or vagus nerve evoked discharge. Iontophoretic application of KYN reduced the action potential discharge evoked by activation of the carotid body chemoreceptors by 52 ± 2% in 5 cells tested. The results demonstrate that excitatory amino-acid receptors are involved in visceral afferent evoked activation of NTS neurons. Furthermore, since both mono- and poly-synaptic inputs were attenuated, these receptors appear to be utilized at multiple levels of afferent integration within NTS.

Cholinergic nerve-mediated excitation in the guinea pig choledochoduodenal junction activated by distension.

The electrical basis of propulsive contractions in the guinea pig choledochoduodenal junction (CDJ), which are triggered by distension, was investigated using intracellular microelectrode recording techniques. The isolated CDJ was placed in a continuously perfused tissue chamber at 37 degrees C. Membrane potential was recorded from smooth muscle cells in either the ampulla or in the upper CDJ (upper junction) regions, which were immobilized by pinning. Distension of the upper junction (20-30 s) by increasing intraductal hydrostatic pressure (mean elevation: 2.0 +/- 0.3 kPa, n = 13) triggered "transient depolarizations" (TDs: < 5 mV in amplitude and 2-5 s in duration) and action potentials in the circular muscle layer of the ampulla. The frequency of TDs in the ampulla was increased from 2.2 +/- 0.2 to 15.9 +/- 2.2 min-1 (n = 13) during distension. Simultaneous impalements of cells in the longitudinal and circular muscle layers in the ampulla revealed that subthreshold TDs in the circular layer were associated with an increased rate of action potential discharge in the longitudinal layer. Atropine (Atr; 1.4 x 10(-6) M) and tetrodotoxin (TTX; 3.1 x 10(-6) M blocked the distension-evoked increase in TD frequency, without affecting the frequency of ongoing TDs. The sulfated octapeptide of cholecystokinin (1-5 x 10(-8) M) increased the amplitude of TDs recorded in the circular muscle layer of the ampulla and increased action potential discharge rate. In separate recordings, radial stretch of the ampulla region increased the rate of discharge of action potentials in the smooth muscle of the upper junction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intrinsic prostaglandins on the spontaneous contractile and electrical activity of the proximal renal pelvis of the guinea‐pig

1. The effects of blocking prostaglandin biosynthesis with indomethacin on the spontaneous electrical and contractile activity recorded in smooth muscle strips of the guinea-pig renal pelvis were examined using standard tension and membrane potential recording techniques. 2. Circumferentially cut strips of proximal renal pelvis contracted more frequently (4.5 +/- 0.2 min-1) than strips cut from the mid region (1.3 +/- 0.2; P < 0.05, n = 5) of the renal pelvis. 3. Indomethacin (1 nM-10 microM) reduced the amplitude and frequency of the contractions of the renal pelvis in a concentration- and time-dependent manner. Contractions were completely abolished in the presence of 30 microM indomethacin. 4. After indomethacin blockade, activation of prostaglandin F2 alpha (PGF2 alpha) receptors with dinoprost (1-100 nM) restored the amplitude and frequency of the spontaneous contractions of renal pelvis. Higher concentrations of dinoprost (> 100 nM-3 microM) increased the contraction amplitude of the proximal and mid renal pelvis 1.9 and 1.6 times respectively. The contraction frequency of the mid renal pelvis, but not the proximal pelvis, was also raised above its pre-indomethacin frequency. 5. The spontaneous electrical activity recorded in proximal strips of the renal pelvis was designated to come from three cell types: (i), pacemaker cells (10% of cells recorded), with simple action potentials comprising relatively slow rising and repolarizing phases triggered on top of a slowly-developing pre-potential; (ii), driven cells (75% of cells), with complex action potentials comprising a rapid initial spike, followed by a period of membrane oscillation and a plateau of 0.2-2 s duration; and (iii), intermediate cells (15%) which fired action potentials with an initial rapid and a long plateau phase. 6. Indomethacin (10-30 micro M) decreased the amplitude and frequency of the action potentials recorded in driven and intermediate cells. The membrane potential of these cells also depolarized 5mV to-51.2 +/-2.6mV (n=5).7. Dinoprost (300 nM-1.5 micro M) increased the rate of action potential discharge, without affecting the membrane potential of driven cells previously exposed to indomethacin (30 micro M).8. These data suggest that the endogenous release of prostaglandins is necessary for the in vitro spontaneous contractile activity recorded in the guinea-pig renal pelvis. Blockade of the synthesis of these prostaglandins appears either to modify the ability of the driven regions of the renal pelvis to fire action potentials or to reduce the coupling of these driven regions to their pacemaker cells.

Synaptic activation of rat supraoptic neurons by osmotic stimulation of the organum vasculosum lamina terminalis.

Intracellular recordings were obtained from neurons of the supraoptic nucleus in superfused explants of rat hypothalamus in vitro. Transient hyperosmotic stimulation of the organum vasculosum lamina terminalis (OVLT) area caused long-lasting increases in the frequency of excitatory post-synaptic potentials and an associated rise in the rate of action potential discharge. Such responses could be evoked by small (less than + 2%) increases in osmolality, but not by isotonic solutions. These results suggest that the OVLT plays a functional role in the osmoregulation of neurohypophyseal hormone release.