Changes In Membrane Resistance Research Articles

Actions of vasodilator nerves on arteriolar smooth muscle and neurotransmitter release from sympathetic nerves in the guinea-pig small intestine.

1. Brief constrictions of arterioles of the isolated submucosa of the guinea-pig small intestine were evoked by stimulation of the perivascular sympathetic nerves. Prior stimulation of vasodilator neurones in the submucosal nerve plexus greatly reduced the constrictor response to sympathetic stimulation. 2. Vasodilator nerve stimulation reduced both the amplitude and rate of decay of the excitatory junction potential (EJP) evoked in the arteriolar smooth muscle by sympathetic nerve stimulation. 3. Computer simulation of the effect of membrane resistance changes on the EJP amplitude indicated that the change in amplitude could not be explained by the fall in membrane resistance alone, suggesting that vasodilator nerve activity reduced neurotransmitter release from the sympathetic nerves.

Relationship between changes of glomus cell current and neural response of rat carotid body

1. Mature rat carotid bodies were harvested and sinus nerve activity was recorded in vitro during superfusion with Ringer saline. Membrane currents of glomus cells were simultaneously recorded using conventional whole cell or perforated-patch whole cell recording. Presumptive glomus cells were identified by the presence of a rapidly activated, voltage-dependent outward current above a threshold of -20 mV. 2. Outward current of presumptive glomus cells was inhibited by tetraethylammonium chloride (TEA) (20 mM) and by verapamil (5-10 microM), consistent with previous studies in which isolated glomus cells were used. Somal capacitance, calculated from the current transient following a step hyperpolarization, was 7.47 +/- 0.54 (SE) pF (n = 52). Membrane resistance for perforated-patch recordings was 820 +/- 187 M omega. 3. In perforated-patch recordings, brief periods of hypoxia (30-45 s) caused a marked increase in nerve activity to 21.6 +/- 2.7 times baseline spiking frequency (n = 59) but no significant change in membrane resistance or outward current. No change in holding current was detected, although the low amplifier gain precluded high-resolution measurement. Similar results were obtained using conventional whole cell recording, except that outward current significantly decreased during hypoxia but failed to recover in the immediate posthypoxia period. 4. TEA (20 mM) rapidly inhibited outward current to 55 +/- 7% (n = 15) of predrug current, but nerve activity only slightly increased to 2.0 +/- 0.3 times baseline spike frequency (n = 15). Brief anoxia (40 s in duration) in the presence of TEA evoked a brisk increase in nerve activity to 30 +/- 13 times baseline frequency (n = 3), demonstrating that organ function was not blocked by TEA. 5. Charybdotoxin (10 nM) significantly reduced outward current by 12.1 +/- 3.0% (n = 11) but did not significantly alter nerve activity, holding current, or membrane resistance. Apamin (100 nM) did not significantly affect nerve activity, membrane resistance, or holding current. Outward current decreased by 11.4 +/- 6.1% (n = 13). 6. These results show a dissociation between changes in glomus cell voltage-gated outward currents and changes in afferent nerve activity. This suggests that modulation of glomus cell K+ current by hypoxia is not the primary step in initiating the nerve response to hypoxia in the rat carotid body.

Non-reciprocal control of rhythmic activity in respiratory-modulated XII motoneurons.

To elucidate the nature of phasic respiratory inputs to hypoglossal (XII) motoneurons, we assessed the phasic changes in membrane resistance (RN) in inspiratory- and expiratory-modulated motoneurons. In expiratory motoneurons, RN was consistently lower in inspiration than in expiration and intracellular injection of negative current reversed the phasic hyperpolarizing membrane potential wave in inspiration. In inspiratory motoneurons, RN changed less but also was minimal in inspiration. In these neurons, injection of a negative current sufficient to reverse a lingual nerve-evoked IPSP did not reverse the phasic expiratory hyperpolarization. Thus, respiratory-related inhibitory inputs are non-reciprocal in inspiratory and expiratory XII motoneurons, with inspiratory motoneurons probably lacking a somatic, amino acid-mediated inhibitory input in expiration.

The electrophysiology of ischemia and cardioplegia: implications for myocardial protection.

The primary goal of modern cardioplegia is to protect the heart during the periods of cardiac arrest and global ischemia that are required to perform cardiac surgery. In order to achieve this, cardioplegic solutions must be able to arrest rapidly the electrical activity of the heart. An understanding of the electrophysiology of cardioplegia is critical to an adequate understanding of its basic mechanisms of action. This article reviews recent advances in our understanding of the electrophysiological changes seen during ischemia and cardioplegia. Although 10 years ago, depolarization and repolarization were attributed to changes in membrane resistance, advances in molecular biology have elucidated that the mechanism of the action potential is governed by ionic transport across hydrophobic lipid membranes through carefully regulated pores formed by members of an extended family of ion channel proteins. There also have been great strides in our understanding of the heart's electrophysiological response to ischemia. One of the most dramatic responses to ischemia is a profound shortening of the cardiac action potential, which has been shown to be cardioprotective by limiting calcium influx into the cell. ATP-sensitive potassium channels have been confirmed to play a critical role in the action potential shortening seen during ischemia. Drugs that open these channels have been shown to limit infarct size, attenuate myocardial stunning, and ameliorate reperfusion injury. Recent work has demonstrated that these drugs may be effective cardioplegic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen depolarizes guinea pig bronchial parasympathetic ganglion neurons by activation of histamine H1 receptors.

Studies were carried out to evaluate the mechanism by which neurotransmission through airway parasympathetic ganglia may be modulated during immediate hypersensitivity reactions. Guinea pigs were passively sensitized by injection of guinea pig serum containing high-titer anti-ovalbumin antibodies. Intracellular recordings were obtained from intrinsic parasympathetic ganglion neurons from the right mainstem bronchus in vitro. Ovalbumin (10 micrograms/ml) elicited a membrane potential depolarization and changes in membrane resistance in bronchial ganglion neurons from passively sensitized guinea pigs. Histamine mimicked the depolarizing effect of ovalbumin in a concentration-dependent manner (0.1-10 microM) and caused a transient increase and decrease in membrane resistance. Pyrilamine, a histamine H1-receptor antagonist, inhibited the histamine-induced membrane depolarization and decrease in resistance. By contrast, blocking histamine H2 and H3 receptors did not inhibit histamine-induced depolarization. Pyrilamine also reduced the antigen-induced depolarization of ganglion neurons, demonstrating a role for histamine H1 receptors in this response. The data provide evidence that the antigen-induced depolarization of airway ganglion neurons is secondary to an antigen-antibody interaction on intrinsic mast cells and the consequential effect of histamine on H1 receptors. These studies demonstrate that histamine released during an immediate hypersensitivity reaction has direct effects on airway parasympathetic nerves.

Use of brain slices in the study of free-radical actions

To understand the neuropathological roles of free radicals we investigate their actions in a model neuronal system, the hippocampal brain slice. Free radicals can be generated through a number of methods: hydrogen peroxide to produce hydroxyl radicals, dihydroxyfumarate to generate superoxide and ionizing radiation producing a variety of radical species. We find that free radicals have a number of profound effects in this system, which can be prevented by free-radical scavengers and antioxidants. With exposure to free radicals, the ability to generate spikes and synaptic efficacy are impaired. Decreased spike generating ability is correlated with lipid peroxidation. No change in membrane potential, membrane resistance, or many of the potassium currents can account for the effect on spike generation. Protein oxidation is likely to underlie synaptic damage. Both inhibitory and excitatory synaptic potentials are reduced by free-radical exposure. Presynaptic mechanisms are implicated. Lower concentrations of radicals prevent the maintenance of long-term potentiation, perhaps through oxidation of the NMDA receptor. The actions of the free radicals are often reversible because of the presence of repair mechanisms, such as glutathione, in hippocampal slices. The brain slice preparation has allowed us to begin to understand the electrophysiological and biochemical consequences of free-radical exposure.

The delayed basolateral membrane hyperpolarization of the bovine retinal pigment epithelium: mechanism of generation.

1. Conventional and ion-selective double-barrelled microelectrodes were used in an in vitro preparation of bovine retinal pigment epithelium (RPE)-choroid to measure the changes in membrane voltage, resistance and intracellular Cl- activity (aCli) produced by small, physiological changes in extracellular potassium concentration ([K+]o). These apical [K+]o changes approximate those produced in the extracellular (subretinal) space between the photoreceptors and the RPE following transitions between light and dark. 2. Changing apical [K+]o from 5 to 2 mM in vitro elicited membrane voltage responses with three distinct phases. The first phase was generated by an apical membrane hyperpolarization, followed by a (delayed) basolateral membrane hyperpolarization (DBMH); the third phase was an apical membrane depolarization. The present experiments focus on the membrane and cellular mechanisms that generate phase 2 of the response, the DBMH. 3. The DBMH was abolished in the presence of apical bumetanide (100 microM); this response was completely restored after bumetanide removal. 4. Reducing apical [K+]o, adding apical bumetanide (500 mM), or removing apical Cl- decreased aCli by 25 +/- 6 (n = 8), 28 +/- 1 (n = 2) and 26 +/- 5 mM (n = 3), respectively; adding 100 microM apical bumetanide decreased aCli by 12 +/- 2 mM (n = 3). Adding apical bumetanide or removing apical bath Cl- hyperpolarized the basolateral membrane and decreased the apparent basolateral membrane conductance (GB). 5. DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) blocked the RPE basolateral membrane Cl- conductance and inhibited the DBMH and the basolateral membrane hyperpolarization produced by apical bumetanide addition or by removal of apical Cl-o. The present results show that the DBMH is caused by delta[K]o-induced inhibition of the apical membrane Na(+)-K(+)-2Cl- cotransporter; the subsequent decrease in aCli generated a hyperpolarization at the basolateral membrane Cl- channel.

Spontaneous bursting induced by convulsant agents in an identified insect neurone

1. 1. Using an in vitro preparation, intracellular recordings were made from the cell body of the “fast” coxal depressor motoneurone ( D f) from the cockroach, Periplaneta americana. 2. 2. This cell was normally quiescent in the absence of injected current but could respond to applied depolarizing current with one or more plateau potentials: regenerative depolarizations which can drive production of axonal impulses. However, when the convulsant agents picrotoxin (PTX; 10 −5 M) or pentylenetetrazole (PeTZ; 25 mM) were applied D f exhibited spontaneous bursting behaviour. 3. 3. The bursting activity induced by the two agents was qualitatively different. The bursting pattern induced by PTX was irregular and occurred only after a delay of 20–40 min; the transformation to bursting activity occurred without any consistent changes in membrane potential and effective membrane resistance ( 5.9 ± 0.4 MΩ; n = 25; mean ± SEM ) remained unchanged ( P > 0.1). PTX did not induce spontaneous bursting or cause a significant change in plateau potential threshold or membrane potential in isolated somata. Therefore, it appeared to exert its actions or more distant regions of the neurone, probably by enhancing the effects of excitatory synaptic input. 4. 4. In contrast, PeTZ rapidly (30 sec-2 min) induced regular bursting activity. This agent could also produce spontaneous bursting activity in isolated somata; thus it exerted its actions primarily upon intrinsic membrane properties, although it also enhanced the effects of electrically driven synaptic stimulation of the non-isolated D f somata. 5. 5. Experiments with PTX also revealed that bursting could be recorded in cells in which it was not possible to evoke plateau potentials by electrically depolarizing the soma. This suggests that other regions of the cell possess the machinery necessary to produce burst-like behaviour.

Receptor-effector coupling pathway for alpha 1-adrenergic modulation of abnormal automaticity in 'ischemic' canine Purkinje fibers.

We studied the receptor-effector coupling mechanism responsible for alpha 1-adrenergic receptor-induced increases in abnormal automaticity (AA) occurring at low membrane potentials in "ischemic" Purkinje fibers, superfused with Tyrode's solution containing [K+]o 10 mmol/L, pH 6.8, PO2 < 25 mm Hg. To exclude beta-adrenergic actions, propranolol was added to all solutions. We derived membrane slope resistance (Rsl) from the current-voltage relation obtained with two microelectrodes for intracellular current injection and transmembrane voltage recording. We also measured the membrane time constant, Tm, to assess changes in membrane resistance (Rm). Phenylephrine effects on Rsl in simulated ischemia were studied in the absence or presence of the alpha 1-subtype blockers WB 4101 (WB) or chloroethylclonidine (CEC), both 0.1 mumol/L, and in Purkinje fibers from dogs injected with pertussis toxin (PTX) (30 micrograms/kg i.v., 60 to 72 hours before study). There were no significant differences in mean values of Rsl before phenylephrine superfusion among all groups of Purkinje fibers. Tm increased by 23% during phenylephrine 0.1 mumol/L superfusion, and Rsl increased by 11%. These two results suggest a 23% increase in Rm with no concordant change in longitudinal resistance. In the presence of CEC, phenylephrine increased Rsl by 12%. In contrast, WB blocked phenylephrine effects on Rsl (0.3%). In PTX-treated Purkinje fibers, the levels of PTX-sensitive G protein as well as phenylephrine effects on Rsl (3%) were significantly reduced. In the absence of WB and of CEC, the phenylephrine effects both on Rsl and on the incidence of AA were directly related to the level of PTX-sensitive substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

K+ and Cl- transport mechanisms in bovine pigment epithelium that could modulate subretinal space volume and composition.

1. Conventional and ion-selective double-barrelled microelectrodes were used in an in vitro bovine retinal pigment epithelium (RPE)-choroid preparation to measure the changes in membrane voltage, resistance and intracellular K+ and Cl- activities produced by small, physiological changes in extracellular potassium ([K+]o). 2. In the intact eye, light-induced changes in [K+]o occur in the extracellular (or subretinal) space that separates the neural retina and the RPE apical membrane. These [K+]o changes can be approximated in vitro by decreasing apical bath [K+]o from 5 to 2 mM. 3. This in vitro change in [K+]o simultaneously decreased intracellular Cl- and K+ activities (aCli and aKi) by 25 +/- 6 mM (n = 8) and 19 +/- 7 mM (n = 4) (mean +/- S.D.), respectively. In control Ringer solution (5 mM [K+]o) aCli and aKi were 65 +/- 10 mM (n = 28) and 65 +/- 8 mM (n = 6), respectively. 4. The [K+]o-induced decreases in aCli and aKi were both significantly inhibited, either by blocking the apical membrane K+ conductance with Ba2+ or the basolateral membrane Cl- conductance with DIDS (4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid). 5. Transepithelial current pulses were used to determine the relative basolateral membrane Cl- conductance, TClBAS, was approximately 0.6 (n = 3), and the relative apical membrane K+ conductance, TKAP, was approximately 0.7 (n = 2). Step changes in basal bath [K+]o were used to estimate the relative basolateral membrane K+ conductance, TKBAS, was approximately 0.34 (n = 3). 6. These data show that the apical membrane K+ conductance and the basolateral membrane Cl- conductance are electrically coupled. In vivo, this coupling could have significant functional importance by modulating the relative hydration of the subretinal space, regulating RPE cell volume, and buffering the chemical composition of the subretinal space.

Small lipid-soluble cations are not membrane voltage probes for Neurospora or Saccharomyces

Small lipid-soluble cations, such as tetraphenylphosphonium (TPP +) and tetraphenylarsonium (TPA +) are frequently used as probes of membrane voltage (ΔΨ, or V m ) for small animal cells, organelles, and vesicles. Because much controversy has accompanied corresponding measurements on ‘walled’ eukaryotic cells (plants, fungi), we studied their transport and relation to V m in the large-celled fungus Neurospora crassa - where V m can readily be determined with microelectrodes - as well as in the most commonly used model eukaryotic cell, the yeast Saccharomyces cerevisiae. We found no reasonable conditions under which the distribution of TPP + or TPA +, between the cytoplasm (i) and extracellular solution (o), can serve to estimate V m , even roughly, in either of these organisms. When applied at probe concentrations (i.e., ≤ 100 μM, which did not depolarize the cells nor deplete ATP), TPP + stabilized at ratios (i/o) below 30 in both organisms. That would imply apparent V m values positive to − 90 mV , in the face of directly measured V m values (in Neurospora) negative to − 180 mV . When applied at moderate or high concentrations (1–30 mM), TPP + and TPA + induced several phases of depolarization and changes of membrane resistance ( R m ), as well as depletion of cytoplasmic energy stores. Only the first phase depolarization, occurring within the perfusion-turnover time and accompanied by a nearly proportionate decline of R m , could have resulted from TPP + or TPA + currents per se. And the implied currents were small. Repeated testing, furthermore, greatly reduced the depolarizing effects of these lipid-soluble ions, implicating an active cellular response to decrease membrane permeability.

Validation of carrier-mediated transport of H + and Na + through mobile-site membranes

The response of membranes containing neutral ion carriers of either H + or Na + to an externally-applied potential step was investigated using previously developed techniques for the analysis of charge and mass transport in ion-selective membranes. The results from constant-resistance membranes, e.g. membranes with unperturbed negative site concentration profiles, showed that tridodecylamine behaved as a carrier for H +, and there was no evidence for proton hopping from stationary carriers. In addition, the experimental outcome supported the assumption of a failure of the Donnan exclusion principle at very low pH levels in these membranes. The results from membranes containing the Na + carrier illustrated the significant concentration polarization of ionic species, which was related to significant changes in bulk membrane resistance.

Evaluation of enhancers to increase nasal absorption using Ussing chamber technique.

The effects of eight prospective absorption enhancers on the nasal mucosa in rabbit have been assessed using an in vitro Ussing chamber technique. Sodium taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl ether (BL-9), lysophosphatidylcholine (LPC) and sodium dodecyl sulfate (SDS) were found to possess relatively high protein leaching activity, while sodium glycocholate (GC), sodium taurocholate (TC) and EDTA had relatively low activity. The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a model drug across the nasal mucosa was found to be greater in the presence of these enhancers. Their enhancement ratio was found to be in the order of BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein leaching activity. The differences in protein leaching and enhancement ratio dependent on the magnitude of change of membrane resistance (delta Rm), indicating that these enhancers damaged the membrane and increased FD permeation. delta Rm thus appears to be a useful indicator by which one can estimate nasal mucosa damage by the enhancers.

Depolarizing Action of Secretory Granule Protein 7B2 on Rat Supraoptic Neurosecretory Neurons

A novel precursor neuropeptide termed 7B2 is present within specific brain areas, including the hypothalamic magnocellular neurosecretory neurons, and appears to be processed to smaller fragments. In order to determine whether specific C-terminal fragments of 7B2 might exert local effects on neurosecretory cells, we used intracellular current-clamp recordings in supraoptic neurons maintained in superfused hypothalamic explants to evaluate membrane potential and resistance changes in 25 supraoptic nucleus neurons during bolus applications of 7B2 174-186 and two other C-terminal peptide fragments 7B2 156-173 and 7B2 141-150. In 15 supraoptic neurons, only the 7B2 174-186 fragment induced a gradual 2-8 mV membrane depolarization that lasted for 4 to 30 min and was accompanied by 15+/-8% reduction in input resistance. Immunocytochemical identification of the recorded cells revealed that both vasopressin (VP)- and oxytocin (OT)-containing neurons were depolarized by 7B2 174-186. These data suggest that 7B2 174-186 is a biologically active fragment of 7B2 and may regulate the excitability of magnocellular supraoptic nucleus neurons.

Properties of composite membranes formed from ion-exchange membranes and conducting polymers. 4. Change in membrane resistance during electrodialysis in the presence of surface-active agents

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProperties of composite membranes formed from ion-exchange membranes and conducting polymers. 4. Change in membrane resistance during electrodialysis in the presence of surface-active agentsToshikatsu SataCite this: J. Phys. Chem. 1993, 97, 26, 6920–6923Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/j100128a029RIGHTS & PERMISSIONSArticle Views317Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts

Immunologically induced neuromodulation of guinea pig nodose ganglion neurons

The influence of specific antigen challenge on the excitability of C-cells in nodose ganglia isolated from actively sensitized guinea pigs was evaluated using intracellular recording techniques. Antigen (ovalbumin) caused a significant depolarization (∼ 8 mV) of the resting membrane potential. Antigen exposure had differing effects on the membrane input impedance; decreasing it in 15 neurons, increasing it in 6 neurons, and having no effect in 8 neurons. About 20% of guinea pig nodose C-cells reveal a long-lasting after-spike hyperpolarization (AHP slow). Antigen challenge reversibly blocked the AHP slow in 4 of 18 neurons studied in 18 ganglia. About 30% of the nodose ganglion neurons display a time- and voltage-dependent inward rectification at membrane potentials more negative than −75 mV. Exposing the ganglion to the sensitizing antigen consistently blocked this response in 8 of 8 neurons. Histological assessment of toluidine blue stained cells revealed that the nodose ganglion contained approximately 100 mast cells. Exposing the ganglion to ovalbumin stimulated mast cell degranulation, as measured by a decrease in number of stained cells, and evoked the release of histamine, PGD2, and immunoreactive peptidoleukotrienes from the tissue. The results support the hypothesis that endogenous inflammatory mediators released during the immediate hypersensitivity (allergic) reactions can modulate the excitability of primary C-fiber afferents. Mechanisms underlying antigen-induced neuromodulation of these neurons include depolarization of the resting membrane potential, changes in membrane resistance, blockade of a time- and voltage-dependent anomalous rectifier, and, in some cells, blockade of the AHP slow.

Monitoring electropermeabilization in the plasma membrane of adherent mammalian cells

When an electrical potential of order one volt is induced across a cell membrane for a fraction of a second, temporary breakdown of ordinary membrane functions may occur. One result of such a breakdown is that molecules normally excluded by the membrane can now enter the cells. This phenomenon, generally referred to as electropermeabilization, is known as electroporation when actual pores form in the membrane. This paper presents a unique approach to the measurement of pore formation and closure in anchored mammalian cells. The cells are cultured on small gold electrodes, and by constantly monitoring the impedance of the electrode with a low-amplitude AC signal, small changes in cell morphology, cell motion, and membrane resistance can be detected. Because the active electrode is small, the application of a few volts across the cell-covered electrode causes pore formation in the cell membrane. In addition, the heat transfer is very efficient, and the cells can be porated in their regular growth medium. By this method, the formation and resealing of pores due to applied electric fields can be followed in real time for anchorage-dependent cells.

Electrophysiological study of neurotropin-induced responses in guinea pig hypothalamic neurons

To investigate the direct actions of neurotropin (NSP, a nonproteinaceous extract from inflamed skin of rabbits which is in therapeutic use), intracellular recordings were made from neurons of the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA) in slices of guinea pig brain. In the VMH, NSP, applied by perfusion (0.1–3.0 NU/ml), caused dose-dependent depolarization in 29 of 48 neurons (60%) tested. No change in membrane resistance was observed during the depolarization, which hypothesized that the NSP-induced depolarization might be mediated through the inactivation of the Na-K. pump. The NSP-induced depolarization persisted even after the elimination of synaptic activity by perfusion with Ca 2+-free and high Mg 2+ Ringer solution. NSP hyperpolarized the cell membrane of three neurons (6%) while two neurons (4%) showed biphasic responses; transient depolarization followed by long-lasting hyperpolarization. Membrane potential of the remaining 14 neurons was not changed by application of NSP. Of 14 LHA neurons tested for NSP effects, eight (57%) were depolarized, three (21%) were hyperpolarized, and one showed a biphasic response. The present results suggest that NSP significantly modulates hypothalamic neuron activity, and the central modulation of autonomic functions by NSP might be mediated through hypothalamic neurons.

Effects of aspirin on pathways of ion permeation in Necturus antrum: Role of nutrient HCO3−

Intracellular microelectrodes were used to evaluate electrical properties of the cell membranes in Necturus antral mucosa during exposure to luminal acid alone (pH 4) or to 5 mmol/L aspirin [acetylsalicyclic acid (ASA)] in the presence of luminal acid. When nutrient solutions were buffered by HCO3− (pH 7.3), ASA moderately depolarized and increased the resistances of both cell membranes. When nutrient solutions were buffered by HEPES (pH 7.3), ASA induced even greater depolarizations of the cell membranes. In addition, resistance of the apical membrane did not increase and resistance of the basolateral membrane decreased. The changes in basolateral membrane resistance were observed when tissues were exposed to 5 mmol/L salicylate but not during exposure to luminal acid alone or to acidified luminal solutions containing 5 mmol/L acetate, a small and permeable organic acid. Electron microscopy confirmed that these initial electrophysiological changes precede alterations in cell morphology. The findings suggest that nutrient HCO3− attenuates changes in membrane potentials caused by ASA. Loss of nutrient HCO3− seems to accelerate alterations in basolateral membrane resistance caused by ASA and its salicylate moiety.

Pacemaker current, membrane resistance, and K+ in sheep cardiac Purkinje fibres.

The pacemaker current in cardiac Purkinje fibres has been attributed to either a decrease in potassium conductance or an increase in a non-specific (Na-K) conductance. The former mechanism would be associated with an increase in membrane resistance (Rm) and the latter with a decrease in Rm. The aim of this study was to obtain evidence in support of one or other mechanism by measuring Rm during the pacemaker current (Idd) under conditions where there is a small or no extracellular potassium depletion. Hearts were obtained from anaesthetised sheep and thin strands of ventricular Purkinje fibres were shortened to less than or equal to 1.6 mm. Purkinje fibres were voltage clamped to potentials positive and negative to the potassium equilibrium potential (EK) using a two microelectrode technique. Small current pulses were superimposed on Idd to measure Rm changes. Procedures were used that decrease either the background potassium current IKl or Idd in order to dissect changes in Rm due to K depletion from those due to Idd. Rm increased during Idd, whether the pacemaker current increased or decreased as a function of time. Increasing [K]o from 2.7 to 5.4 mmol.litre-1 decreased Rm and during hyperpolarising steps increased the instantaneous current but did not change Idd amplitude. In 2.7 mmol.litre-1 K, caesium (Cs, 2 mmol.litre-1) increased the holding current (Ih), had little effect on the instantaneous current, and eliminated Idd and associated Rm changes. In 5.4 and 10.8 mmol.litre-1 K, Cs increased Ih and decreased Idd amplitude and in 10.8 mmol.litre-1 K Cs decreased the instantaneous current on hyperpolarisation. If the current was reversed, Cs decreased but did not abolish it. In normal [K]o, barium (Ba, 0.05-0.5 mmol.litre-1) increased Ih and Rm, reduced the instantaneous current but did not increase Idd amplitude. In high [K]o, Ba instead increased the amplitude and rate of development of Idd. When Cs was applied in the presence of Ba, Idd was reduced or eliminated depending on [K]o. The changes in membrane resistance during the pacemaker current cannot be accounted for by K depletion and suggest that in the range of diastolic depolarisation the pacemaker current results predominantly from a time dependent decrease in K conductance.