Low Stimulation Rates Research Articles

Optical measurements of activity-dependent membrane recycling in motor nerve terminals of mammalian skeletal muscle

Motor nerve terminals in a variety of rat and mouse skeletal muscles were stained in an activity-dependent fashion using the styryl dyes FM1-43 or FM2-10. Low-light video microscopy and digital image processing techniques were used to evaluate destaining of the preparations during application of depolarizing stimuli. Best results were obtained with the mouse triangularis sterni muscle. Quantitative analysis of the destaining of dye-loaded terminals supports the suggestion that FM1-43 stains a recycling membrane compartment, most probably synaptic vesicles. However, the pattern of staining and destaining were not the same as those reported previously for frog neuromuscular junctions. The pattern of nerve terminal staining was less punctate and the rate and amount of activity-dependent destaining were less than in frog muscle. Part of the explanation may be a more acute susceptibility of mammalian terminals to phototoxicity.

Repletion of sarcoplasmic reticulum Ca after ryanodine in rat ventricular myocytes.

The ryanodine (R)-induced loss of sarcoplasmic reticulum (SR) Ca2+ and the abilities of the SR to accumulate Ca2+ and participate in contractile activation after R were studied in rat ventricular myocytes. Indo 1 fluorescence (IF) indexed cytosolic Ca2+, and caffeine assayed SR Ca2+. Before R, there was a negative staircase, and the SR accumulated Ca2+ at rest. During stimulation (0.5 Hz), R decreased IF and contraction, converting the negative staircase to positive. When R was pulsed onto resting cells, IF increased and cells shortened, subsequently behaving as if stimulated in R. After R, there was no caffeine-releasable Ca2+ at rest, and little accumulated during 0.5-Hz stimulation. At high rates, caffeine-releasable Ca2+ and diastolic IF increased. In isoproterenol and R, IF transients and contractions recovered at 0.5 Hz with a marked positive staircase and little diastolic IF increase. Within 10 beats, SR Ca2+ accumulated to pre-R levels. R eliminated the positive inotropic effect of paired-pulse stimulation, but isoproterenol temporarily restored it. Twitch contractions in thapsigargin, an SR Ca2+ pump blocker, and isoproterenol were slow compared with control or R + isoproterenol. R leaks SR Ca2+ into the cytosol. SR Ca2+ can be repleted in R by high-rate stimulation or by low-rate stimulation with a beta-adrenergic agonist. SR Ca2+ release in R can be temporarily restored if Ca2+ influx and SR Ca2+ pumping are increased enough to overcome the SR Ca2+ leak.

Age related changes in contractility and 1 adrenergic responsiveness of myocardium from normal hamsters and hamsters with hereditary cardiomyopathy

The aim was to evaluate age related changes in myocardial contractility and alpha 1 adrenergic responsiveness in myocardium from normal and cardiomyopathic hamsters. 50 male cardiomyopathic hamsters (CHF 147) and 45 golden Syrian hamsters were killed at 30, 50, 100, 200, or 300 days of age. Left ventricular papillary muscles were isolated and mounted in an isolated bath and isometric, isotonic, and unloaded contractions were recorded during a phenylephrine dose-response curve. The effects of increasing stimulation rate from 6 to 45 x min-1 and of increasing temperature from 29 degrees C to 35 degrees C before and after the addition of phenylephrine were verified in 100 day old hamsters. At 30 days of age, tension generation and shortening indices were similar in both strains. Thereafter, contractility increased in normal hamsters, to reach a peak at 50 d which was maintained until 300 d, when a slight decrease occurred. In cardiomyopathic hamsters, contractility increased more slowly, such that by 50 d tension was lower than in normals, at 15.8(SEM 1.9) v 26.5(2.2) mN.mm-2 (p < 0.01). This decrease persisted until 200 d, when it normalised and then decreased again by 300 d. The response of normal and cardiomyopathic muscles to phenylephrine was similar at 30 days of age. Thereafter, the response of cardiomyopathic muscles decreased more than in normals. This decrease was accompanied by a rightward shift in the dose-response curve. Increasing stimulation rate had no effect under basal conditions; however, once phenylephrine was added it caused tension to increase in cardiomyopathic muscles instead of decreasing, thereby rendering the relative effects of phenylephrine at 45 stimuli.min-1 similar in both groups. Force generating and shortening indices in normal and cardiomyopathic hamster myocardium are similarly immature at 30 days of age. Normal myocardium reaches its full potential by 50 d, but cardiomyopathic myocardium does not reach it until 200 d, and it decreases thereafter. A decrease in alpha 1 adrenergic responsiveness in cardiomyopathic myocardium at lower stimulation rates can be reversed by increasing the stimulation rate.

GABA A receptor-mediated mechanisms contribute to frequency-dependent depression of IPSPs in the hippocampus

Intracellular recordings from in vitro guinea-pig hippocampal slices were obtained to investigate the mechanisms underlying activity-dependent depression of inhibitory postsynaptic potentials (IPSPs) in Ca1 pyramidal neurons. IPSPs were studied following blockade of glutamatergic transmission. Attenuation of both fast and slow IPSP components was apparent at stimulus rates of >0.2 Hz, but the late IPSP showed depression at even lower rates of stimulation. Overlap of these events made resolving response components during depression difficult. Fast IPSPs were isolated using CsCl-filled microelectrodes, blocking slow potassium-dependent IPSPs and reversing the chloride gradient. Under this condition repetitive stimulation did not induce IPSP depression. Other experiments showed slow IPSP depression at stimulus rates of <0.5 Hz was relieved in the presence of picrotoxin which antagonizes GABA A events. These results suggest that activity-dependent depression of the fast IPSP results largely from chloride accumulation as a consequence of repetitive activation. Depression of the slow IPSP appears to arise from at least two components: (1) a masking of the slow hyperpolarization resulting from an apparent increase in the depolarizing GABA response due to chloride accumulation; and (2) a novel process involving GABA A receptors, perhaps mediated through presynaptic inhibition.

Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit.

1. Conventional microelectrode techniques were used for intracellular recordings of the transmembrane electrical potentials, the effects of berberine were studied on canine cardiac Purkinje and ventricular muscle fibres and on rabbit atrial fibres. 2. Berberine (3-30 microM) increased in a concentration-dependent manner, the action potential duration (APD) in canine Purkinje and ventricular muscle without affecting other parameters of the action potential. 3. The berberine-induced enlargement of the APD showed reverse use-dependence, so that the effect was greater at lower rates of stimulation. 4. Preparations perfused with berberine (30 microM) and driven at rates below 0.5 Hz exhibited early after depolarizations which persisted 3-4 h after washing. 5. The early afterdepolarizations were reversibly abolished by perfusion with lignocaine (3 microM) or by the increase in the rate of stimulation. 6. The effective refractory period (ERP) of Purkinje fibres was greatly increased by berberine (30 microM); however, the ratio ERP/APD was not significantly affected. 7. Berberine (10-100 microM) decreased in a concentration-dependent manner the spontaneous frequency of rabbit sinoatrial cells. The decrease in frequency was accompanied by a depression of the phase 4 depolarization, without significant changes in other parameters of the nodal action potential. 8. Atropine (2.5 microM) did not affect the bradycardic effect of berberine. On the other hand, berberine (30 microM) did not alter the chronotropic effect of isoprenaline. 9. Berberine (30 microM) also increased the duration of slow responses in K-depolarized rabbit atrial muscle fibres, other parameters being unaffected. 10. It is suggested that berberine exerts Class III antiarrhythmic and proarrhythmic actions in cardiac muscle of the dog in vitro.

Auditory brainstem responses recorded at fast stimulation rates using maximum length sequences.

There are now commercially available systems which can provide maximum length sequence averaging techniques. This study examines the effects on auditory brainstem response amplitude and latency of using such a system and stimulating at rates from 9 to 1000 clicks/s. As expected there is considerable adaptation of the response such that at 1000 clicks/s wave V amplitude is only approximately 8% of its low stimulation rate value. As the stimulation rate is increased so the test time taken to obtain a response of the same signal-to-noise ratio as a conventional recording decreases. This process continues up to a maximum click rate of about 200 clicks/s. Thereafter, the response adapts so rapidly that further increases of rate lead to a worsening of performance. Thus, the optimum stimulation rate appears to be of the order of 200 clicks/s and this can give a speed improvement by a factor of approximately 2.8 over conventional recordings taken at 9 or 10 clicks/s.

Sarcoplasmic reticulum and excitation-contraction coupling at 20 and 10 �C in rainbow trout myocardium

Isometric force and series membrane potential were recorded in isolated ventricular strips from rainbow trout at 20 and 10 °C. Preparations were electrically stimulated to contract at either 0.5 or 0.2 Hz. Single extrastimulations elicited a twitch force which diminished when the preceding diastole was shortened below the regular value. The stimulation following this extra stimulation evoked no potentiation of force. Apart from a marginal effect on the post extrasystolic force at 20 °C, ryanodine did not affect either of these responses or the steady-state force at 0.5 Hz. At 0.2 Hz the steady-state force was somewhat depressed by ryanodine at 20 but not at 10 °C. In contrast, extrastimulations preceded by diastoles of up to 1 h more than doubled extrasystolic force at 20 °C. This effect was removed by ryanodine. Both the potentiations and the effect of ryanodine were strongly reduced at 10 °C. Apparently, temperature acts on the release of Ca2+ from the sarcoplasmic reticulum, since Ca2+ seems to be taken up at both temperatures. Hence, at both 20 and 10 °C, the contractures evoked in a solution inhibiting sarcolemmal Ca2+ transfer and releasing Ca2+ from the sarcoplasmic reticulum were diminished by pretreatment with 15 mM caffeine. Action potential duration at 20 °C was less than half of that at 10 °C. At both temperatures it tended to be prolonged by periods of prolonged rest. No effect of ryanodine on action potential configuration was detected. The results suggest that trout myocardial sarcoplasmic reticulum, although powerful at unphysiologically low stimulation rates, does not partake in the beat-to-beat regulation of force at heart rates encountered in vivo.

Brainstem auditory evoked responses in infants and children with AIDS

Brainstem auditory evoked responses were measured in 16 infants and children with acquired immunodeficiency syndrome (AIDS) and in 9 normal infants and children. Two stimulation rates were used: a conventional rate of 10 Hz and a high rate of 50 Hz. Latencies of waves III, IV, and V on the left were significantly longer in the AIDS group when a stimulation rate of 10 Hz was used. With a higher stimulation rate of 50 Hz, significant differences between the two groups occurred in the latencies of waves I, III, and V bilaterally, but there were no significant differences in the interpeak latencies. A measure of the differential effect of the increasing stimulus rate on the two groups was significant for wave I latency and for I–III and I–V interpeak latencies on the left, revealing that increasing stimulation rate prolongs these measures more in the AIDS group. Increased brainstem auditory evoked response stimulation rate may unmask abnormalities in infants and children with AIDS that are not observed when the lower stimulation rate is used.

Données électrophysiologiques dans les syndromes myasthéniformes de type Lambert-Eaton. À propos d'une série de 23 cas

The electrophysiological data of 23 adult patients with Lambert-Eaton myasthenic syndrome (LEMS) have been reviewed. Lung carcinoma was disclosed in 17. In six cases with an EMG follow-up ranging between one and 17 years no carcinoma was detected. The results of repetitive nerve stimulation test (RNS) were not statistically different between the 2 groups. Low CMAP ulnar amplitude was present in all patients (mean: 1.7 mV). Decremental response at low rate of stimulation (3 Hz) was present in 17/20 (means: 30%). An abnormal incremental response at high rate of stimulation was present in all cases (mean: 826%). The authors emphasize the interest of a 50 Hz stimulation for 4 s. Increase of the 'F-wave' amplitude was noticed in some cases. Electrophysiological changes suggestive of an associated mild neuropathy were noticed in eight patients but H-reflex was present in 3/3 cases. SFEMG abnormalities were found in 6/6 cases. In one case, stimulated SFEMG showed more blockings and an increased jitter with low rate of stimulation. In one case the electrical pattern of RNS could be misinterpreted as myasthenia gravis in one tested muscle only. The author's results suggest that CMAP amplitude and RNS test could be used to appreciate the short-term improvement of LEMS with treatment and in some cases for the long-term follow-up.

Modeling the dynamic features of the electrogenic Na,K pump of cardiac cells

The purpose of this paper is to examine the dynamic features of the electrogenic Na,K pump of cardiac cells, based on a comparative analysis of a mechanistic model and an ad hoc mathematical description of the Na,K pump. Both representations are incorporated into a modified version of the Beeler-Reuter model for the ventricular membrane, and the resulting action potential models are studied under conditions of repetitive stimulation at steady rates between 0 and 3 Hz. The two Na,K pump representations have nearly identical steady-state characteristics of sensitivity to internal Na+ concentration, external K+ concentration, and membrane potential. Rapid voltage-dependent transient pump currents are present in the mechanistic model, while they are absent in the ad hoc mathematical description we used. The stimulation results show that a sizable peak of pump current caused by the action potential upstroke in the mechanistic model affects phase 1 repolarization, and that this effect is relatively independent of the stimulation rate. The pump current generated by our ad hoc mathematical description is constant during the action potential and does not affect directly the repolarization time course. While the two Na,K pump models show similar pumping efficiency at low stimulation rates, the mechanistic pump is more efficient at high rates of activity. In essence, the distinctive features of the mechanistic model are due to an energy barrier expressing the voltage dependence of the translocation step of the mechanism, and to the redistribution of the intermediates of the biochemical reactions during activity. In comparison, the ad hoc mathematical description exhibits a fixed dependence of the pump current on voltage and ionic concentrations.

Energetics of calcium cycling in nonfailing and failing human myocardium.

Using sensitive antimony-bismuth thermopiles, isometric force and heat output were measured in muscle strips from nonfailing human hearts and from failing dilated cardiomyopathic hearts at a stimulation rate of 60 beats per minute (37 degrees C). This frequency was chosen because analysis of the force-frequency relation showed significant differences in isometric force between failing and nonfailing human myocardium at 60 beats per minute and at higher frequencies, whereas at lower rates of stimulation (30 beats per minute) force of contraction was similar in failing and nonfailing myocardium. The liberated initial heat was partitioned into its two components, tension-dependent heat and tension-independent heat from high-energy phosphate hydrolysis by contractile proteins and excitation-contraction coupling processes, respectively. Tension-dependent heat reflects the total number of crossbridge interactions, and tension-independent heat is an index of the amount of calcium cycling during the contraction-relaxation cycle. In failing compared to nonfailing human myocardium, peak twitch tension, maximum rate of tension rise and maximum rate of tension fall were reduced significantly. Reduced mechanical performance was associated with reduced liberation of both tension-dependent and tension-independent heat in the failing heart. The reduction of tension-dependent heat by 61% and of tension-independent heat by 69% indicate considerable decreases in the number of crossbridge interactions activated and calcium ions cycled during the isometric twitch. In addition, the rate of calcium removal was reduced in the failing human heart as is indicated by a 71% reduction in tension-independent heat rate. The efficiency of excitation-contraction coupling with respect to crossbridge activation was similar in failing and nonfailing myocardium. These data indicate that impaired myocardial performance in dilated cardiomyopathy may result from disturbed excitation-contraction coupling with reduced amount of calcium cycling and reduced rate of calcium removal.

Regional variations in action potentials and transient outward current in myocytes isolated from rabbit left ventricle.

1. Regional variations in the shape of early repolarization of the action potential have been correlated to differences in transient outward K+ current, I(t), in myocytes isolated from the epicardial surface, the endocardial trabeculae and the papillary muscles of rabbit left ventricles. Temperature was 35 degrees C during whole-cell, and 22-23 degrees C during cell-attached experiments. 2. Membrane resting potentials were very similar regionally. At 0.1 Hz stimulation the action potential plateau amplitude in papillary muscle cells was significantly higher (104.7 mV) than in epicardial cells (96.47 mV). Exposure to 4-aminopyridine or increases in the rate of stimulation from 0.1 Hz to 3.3 Hz increased plateau height and diminished the initial notch on repolarization. These effects were correlated to the magnitude of I(t) in these cells. At low rates of stimulation I(t) caused a 'spike and dome' morphology of the action potential. 3. Voltage clamp experiments confirmed a higher current density of I(t) in epicardial cells (7.66 pA/pF at +20 mV) than in endocardial (6.45 pA/pF) or papillary muscle cells (3.69 pA/pF). I(t) at 35 degrees C was faster and larger than previously reported and individual currents inactivated almost completely during 100 ms pulses to plateau potentials. No differences in the kinetics or voltage dependence of whole-cell currents were found. Thus, the half-inactivation potential was -37.8 mV in cells from all three regions. 4. Cell-attached recordings from endocardial and epicardial cells showed very similar single-channel amplitudes, burst open probabilities and ensemble averages. The peak channel open probability soon after the start of depolarizing voltage clamp pulses did not change between cell types (P approximately 0.8). The slope conductance of I(t) channels was 13.0 pS with an intercept near the resting potential of the cell. 5. We conclude that regional variations in the shape of initial repolarization in cells from rabbit left ventricle are caused by variations in the magnitude of the transient outward K+ current, I(t). Epicardial cells have the largest, and papillary muscle cells the smallest I(t). The differences are not explained by alterations in the whole-cell kinetics or single-channel kinetics and conductance. The most likely explanation for variations in whole-cell current density is therefore a decrease in channel density in endocardium and papillary muscle compared with epicardial tissue. We estimate the density of I(t) channels per cell to be 1495 (one per 3-4 micron2) in epicardium, 1175 (one per 4-5 micron2) in endocardium, and 875 (one per 6 micron2) in papillary muscle cells.

Alpha‐adrenergic modulation of the transient outward current in rabbit atrial myocytes.

1. A whole-cell voltage-clamp technique has been used to study the alpha-effects of the adrenergic agonists noradrenaline, methoxamine and phenylephrine on the action potentials and membrane currents of rabbit atrial myocytes. Experiments were carried out at 22-23 degrees C. 2. In the presence of 10(-6) M-propranolol, all three agents prolonged action potential duration. This change could be ascribed principally to changes in membrane current early during the plateau phase of the action potential. In the presence of 10(-3) M-4-aminopyridine, no changes in calcium current (ICa) were observed on exposure to alpha-agonists. No significant shift in the voltage dependence or change in the amplitude of the calcium current-voltage relation was observed. 3. Exposure to 3 x 10(-4) M-CdCl2 to block ICa reduced the action potential prolongation caused by alpha-adrenergic agonists. Measurement of unloaded cell shortening revealed that action potential prolongation caused by alpha-agonists, especially at low stimulus rates, could contribute significantly to the positive inotropic effect of alpha-adrenoceptor stimulation. 4. The voltage-activated transient outward current (It) was markedly reduced during exposure to alpha-adrenergic agonists in a dose-dependent manner in the presence of CdCl2 (3 x 10(-4) M) and propranolol in sufficient concentration to prevent beta-adrenoceptor activation. Noradrenaline exhibited a higher potency for this effect than either methoxamine or phenylephrine. The noradrenaline concentration required to give 50% of the maximal effect was 6 x 10(-6) M compared with 2.3 x 10(-4) M for methoxamine. Noradrenaline reduced It by only about 60% of the maximum reduction produced by methoxamine suggesting that it could be classified as a partial agonist for this effect. 5. The reduction of It during exposure to alpha-adrenergic agonists was rate dependent in that larger current reductions were observed at very low rates of stimulation (less than 0.1 Hz). 6. The magnitudes of current-voltage relations for It were reduced over the entire voltage range studied during exposure to alpha-adrenergic agonists and reductions were dose dependent. No shift of these relations along the voltage axis was observed. 7. The steady-state inactivation relations for It were studied using two voltage clamp protocols. A two-step method resulted in a relatively steep sigmoid 'quasi-steady-state' relation. The half-inactivation potential of -27 mV was unaffected by alpha-adrenergic agonists.(ABSTRACT TRUNCATED AT 400 WORDS)

Glutamate as the Principal Mossy Fibre Transmitter in Rat Cerebellum: pharmacological evidence.

To examine the possibility that glutamate may be widely used as the transmitter for cerebellar mossy fibres, population responses of granule cells following electrical stimulation of these fibres were recorded in rat cerebellar slices using a gap technique. Several different vermal lobules (II, V, VIb, VIII, IXc and X) whose main mossy fibre afferents originate in different nuclei, were compared. The mossy fibre response was remarkably similar in appearance in all lobules. With 1.2 mM Mg2+ in the perfusing solution, and with a low rate of stimulation (0.05 Hz), the N-methyl-D-aspartate (NMDA) antagonist, D-2-amino-5-phosphonovalerate (APV, 30 microM), had little or no effect but all components of the response could be inhibited by the broad spectrum excitatory amino acid antagonist, kynurenate (3 mM), or by the relatively selective non-NMDA antagonist, 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX, 10 microM). Slow APV-sensitive components emerged during high frequency stimulation (30 - 150 Hz) or, with a low stimulation rate, on removal of Mg2+ or addition of bicuculline (30 microM). The results suggest that an excitatory amino acid, presumably glutamate, is the major mossy fibre transmitter in the cerebellum and that it activates both NMDA and non-NMDA receptors on granule cells.

Excitability changes in the crustacean motor axon following activity

It has been shown experimentally that the crustacean motor axon is supernormally excitable following a train of action potentials (Zucker 1974). Such a phenomenon can lead to recruitment of terminals which are unexcited at low rates of stimulation. Although currents underlying the crustacean motor axon have been characterized (Connor et al. 1977), it is not known whether this membrane model accounts for a supernormal period, what might cause superexcitability in this model, or how excitability might change during repetitive stimulation. In present study, it is demonstrated that the crustacean motor axon model does predict a supernormal period, that the supernormal period results from slow recovery from inactivation of the transient potassium, or A, current, and that supernormal excitability is enhanced by repetitive stimulation.

Filter Effects and Low Stimulation Rate on the Middle-Latency Response in Newborns

Auditory middle-latency responses (MLR) have been recorded in 25 newborns at 60 dB nHL using two wide band-pass filter conditions and a slow stimulation rate of 2/s. With both types of filter, the MLR consisted in an initial positive wave followed by a negative component (Na) and a positive component (Pa). In newborns, this positive component appears in the vicinity of 45 ms and is more prolonged than the Pa of the MLR in adults. The probability of obtaining MLR after averaging only 500 signals was higher with a high-pass filter setting of 10 Hz (12 dB/octave), as compared with 5 Hz (12 dB/octave). No significant differences were found in the detectability rate of MLR between the two-filter band-pass settings. It is important to note that some MLR were unstable and not easily replicable. Therefore, the clinical application of these components is still doubtful.

Effects of selective cholinergic antagonists and alpha,beta-methylene ATP on guinea-pig urinary bladder contractions in vivo following pelvic nerve stimulation.

1. An in vivo preparation measuring functional detrusor muscle strength in terms of intravesical bladder pressure (Pves) following in situ pelvic nerve stimulation has been developed in urethane-anaesthetized guinea pigs. 2. The increase in bladder pressure following pelvic nerve stimulation was abolished by topical lidocaine or tetrodotoxin, suggesting a neurogenic origin for the in vivo contractile response. 3. Cholinergic antagonists (i.v.) decreased the amplitude of the peak pressure response by about 50% at both high (30 Hz) and low (5 Hz) stimulation rates, with a rank order of potency of atropine greater than propantheline greater than oxybutynin greater than hexahydrosiladifenidol greater than pirenzepine greater than methoctramine. 4. The P2 purine receptor antagonist, alpha,beta-methylene ATP (i.v.), antagonized pelvic nerve-stimulated bladder contractions differentially at 5 and 30 Hz. At low frequencies, alpha, beta-methylene ATP was both more potent (2.5-fold) and more efficacious (-77 compared to -55% delta) than at 30 Hz. Atropine and alpha,beta-methylene ATP together completely inhibited the contractile response. 5. Together, the findings indicate that in guinea pigs, urinary bladder contractions induced by pelvic nerve stimulation in vivo may be mediated by both muscarinic and purinergic receptors and that these bladder contractions may be mediated by the M2 beta subtype rather than by M1 or M2 alpha muscarinic receptors.

Evidence that atp and noradrenaline are released during electrical field stimulation of the rat isolated seminal vesicle

The effects of electrical field stimulation (at 1–100 Hz with 20–25V supramaximal, and 0·2 ms pulse duration, for 10–20 s), on tone and contractility of rat isolated seminal vesicle was studied, in the absence and presence of specific antagonists (phentolamine, 1 μ M, α,β-Me-ATP, l0μ M, and verapamil, 1 μ M). The aim was to provide pharmacological evidence of the release of ATP, alongside NA, during electrical stimulation of the rat seminal vesicle. Electrical field stimulation of the rat seminal vesicle produced frequency-dependent contractions. At low rates of stimulation (1–20 Hz), only small tonic contractions were observed (0 · 3 g tension), whereas at high rates of stimulation (80–100 Hz), only phasic contractions (2–3 g) were seen. However, at intermediate rates of stimulation (e.g. 50 Hz), a biphasic response was produced: an initial fast, twitch-like response (phasic), followed by a slow tonic contraction. The phasic contraction was blocked by the stable analogue of ATP (α,β-Me-ATP), which desensitizes P 2-purinoceptors. The tonic contraction is adrenergic and was blocked by phentolamine. Verapamil reduced both types of contractions in this preparation and the block was unselective on tonic versus phasic contraction. It was concluded that electrical field stimulation produced frequency-dependent contractions (tonic and phasic) in the rat seminal vesicle. These responses were blocked by specific antagonists, suggesting the presence of different types of neurotransmitters released during electrical stimulation of the rat seminal vesicle.

Diverse electrophysiological spectrum of the Lambert-Eaton myasthenic syndrome.

Among 13 patients with the Lambert-Eaton myathenic syndrome (LEMS), three different patterns on the repetitive nerve stimulation test were observed at the time of initial testing. Type 1 pattern, seen in one patient, had low normal CMAP amplitude, decremental response at the low rate of stimulation (LRS), and relatively normal response at the high rate of stimulation (HRS). Type 2, seen in nine patients, had the classical triad: low CMAP amplitude, decremental response at LRS, and incremental response at HRS. Type 3, seen in three patients, showed low CMAP amplitude, decremental response at LRS, and initial decremental response at HRS. We believe that these three patterns represent different degrees of blocking in LEMS, from the mildest in type 1 to the most severe in type 3. Since types 1 and 3 can be misinterpreted as myasthenia gravis patterns, they must be recognized in LEMS and an incremental response documented by prolonged stimulation at HRS.

Sympathetic transmission in small mesenteric arteries from the rat: highly calcium‐dependent at low stimulation rates

In the present study we examine the calcium requirements of the neurogenic response in vitro of small arteries (150-200 microns diameter) from the mesentery of Wistar rats. Intramural nerves were activated with electrical field stimulation. Responses to single impulses and to low-frequency repeated stimulation were reduced or abolished by reducing the Ca2+ concentration in the bathing solution from 2.5 to 1.0 mM. Responses to higher frequencies (16 Hz) were only slightly affected. Since calcium reduction had markedly less effect on responses to direct activation of the smooth muscle and on responses to any dose of exogenous noradrenaline, the calcium reduction had mainly pre-junctional effects. The data show that part of the neurogenic response is highly calcium-sensitive, perhaps more so than would be expected of a purely noradrenergic transmission.