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PubMed1988

Early effects of parathyroid hormone on membrane potential of rat osteoblasts in culture: role of cAMP and Ca2+.

Microelectrodes were used to investigate the possible involvement of cAMP and Ca2+ ions in the parathyroid hormone's, bPTH(1-34), effect on the membrane potential of rat osteoblasts in primary culture. Parathyroid hormone (10(-7) M) depolarized cell membrane by 25.0 +/- 6.1 mV (mean +/- standard deviation, SD; n = 17). Blocking Ca2+ influx with the Ca channel blocker cobalt revealed two phases in the hormone effect: a rapid and slight membrane hyperpolarization followed by sustained depolarization. In addition, cobalt significantly (p less than 0.01) decreased the magnitude of the PTH depolarizing action. The addition of dibutyryl-cAMP (10(-3) M) to the perfusion solution also resulted in a biphasic effect. At a lower concentration (10(-4) M), dibutyryl-cAMP produced only membrane hyperpolarization, suggesting a cAMP dose dependence of the opposite membrane potential changes. Forskolin (10(-5) M) and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) (10(-4) M) mimicked the depolarizing effect of PTH. IBMX at a low concentration (5 x 10(-6) M) potentiated the depolarizing effect of PTH. Increases in [Ca2+]i using Ca2+ ionophore A23187 and intracellular injection of CaCl2 or inositol trisphosphate decreased the PTH depolarizing action, whereas intracellular injection of EGTA enhanced this effect. These results indicate that PTH evokes a biphasic change in rat osteoblast membrane potential that seems to be mediated by an increase in cAMP and modulated by intracellular calcium.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons.

Short-lasting application (10 min) of tachykinin neuropeptides evokes long-lasting (>24 h) modulation of N-methyl-D-aspartate (NMDA)-evoked locomotor network activity in the lamprey spinal cord. In this study, the net effects of the tachykinin substance P on the isolated spinal cord have been examined by recording from motor neurons in the absence of NMDA and ongoing network activity. Brief bath application of substance P (30 s to 2 min) induced irregular membrane potential oscillations in motor neurons. These oscillations consisted of depolarizing and hyperpolarizing phases and were associated with phasic ventral-root activity. The oscillations were blocked by the tachykinin antagonist spantide II. They were also blocked by tetrodotoxin (TTX), suggesting that they were not dependent on intrinsic membrane properties of the motor neurons but were synaptically mediated. Substance P could also have a direct effect, however, because a membrane potential depolarization persisted in the presence of TTX. Protein kinase agonists and antagonists were used to investigate the intracellular pathways through which substance P acted. The oscillations were blocked by the selective protein kinase C (PKC) antagonist chelerythrine. However, the TTX-resistant membrane potential depolarization was not significantly affected by blocking PKC. The protein kinase A and G antagonist H8 did not affect either the oscillations or the direct TTX-resistant membrane potential depolarization. The glutamate receptor antagonist kynurenic acid abolished the substance-P-evoked oscillations, suggesting that they were dependent on glutamate release. The oscillations were abolished or reduced by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione but were only reduced by the NMDA receptor antagonist D-AP5. The oscillations were thus mediated by glutamatergic inputs with a greater dependence on non-NMDA receptors. Blocking glycinergic inputs with strychnine resulted in large depolarizing plateaus and bursts of spikes. The glutamatergic and glycinergic inputs underlying the oscillations are apparently evoked through direct and indirect excitatory effects on inhibitory and excitatory premotor interneurons. Substance P thus has a distributed excitatory effect in the spinal cord. While it can activate premotor networks, this activation alone is not able to evoke a coordinated behaviorally relevant motor output.

Animals↗
PubMed1995

Influence of magnesium salts on the membrane potential of human endothelial placental vessel cells.

Magnesium salts have been shown to depolarize the membrane of the smooth muscle cells of human placental arteries and veins with and without endothelial cells. In the present study, the influence of MgCl2 and MgSO4 was investigated on the membrane potential, Um, of the endothelial cells of the same vessels. Um was classically recorded with microelectrodes. The endothelial cell membrane of arteries was depolarized by MgCl2 (depolarization threshold, d th: 4 mM) and by MgSO4 (d th: 8 mM). A depolarization was also observed with the endothelial cell membrane of veins. The depolarization threshold with MgCl2 and 4MgSO4 was respectively 6 mM and 8 mM. The different thresholds indicate that the influence of MgCl2 on the endothelial cell membrane potential is higher and more direct than that of MgSO4, and confirm previous hypothesis on the effects of magnesium salts on the vascular smooth membrane cells.

Electric Stimulation↗
PubMed1976

Interactions of membrane potential and cations in regulation of ciliary activity in Paramecium.

Ciliary activity in Paramecium was investigated in different external solutions using techniques of voltage clamp and high frequency cinematography. An increase in the external concentration of K, Ca or Mg ions decreased the resting potential. It had no effect on ciliary activity. When the membrane potential was fixed, an increase in external Ca or Mg and, to a lesser extent, an increase in K concentration, raised the frequency of normal beating or decreased the frequency of reversed beating of the cilia. Similar effects resulted from membrane hyperpolarization with constant ionic conditions. Increase in concentration of Ca, but not of Mg or K, enhanced hyperpolarization-induced augmentation of ciliary frequency. Increase in Ca concentration also specifically augmented the delayed increase in inward current during rapid hyperpolarizing clamp. The results support the view that [Ca]i regulates the frequency and direction of ciliary beating. It is suggested that the insensitivity of the ciliary motor system to elevations of the external concentrations of ions results from compensation of their effects on [Ca]i. Depolarization itself appears to increase [Ca]i while elevation of the external ion concentrations at a fixed membrane potential appears to decrease [Ca]i.

Animals↗
PubMed2003

Membrane potential stabilization in amphibian skeletal muscle fibres in hypertonic solutions.

This study investigated membrane transport mechanisms influencing relative changes in cell volume (V) and resting membrane potential (E(m)) following osmotic challenge in amphibian skeletal muscle fibres. It demonstrated a stabilization of E(m) despite cell shrinkage, which was attributable to elevation of intracellular [Cl(-)] above electrochemical equilibrium through Na(+)-Cl(-) and Na(+)-K(+)-2Cl(-) cotransporter action following exposures to extracellular hypertonicity. Fibre volumes (V) determined by confocal microscope x z - scanning of cutaneous pectoris muscle fibres varied linearly with [1/extracellular osmolarity], showing insignificant volume corrections, in fibres studied in Cl(-)-free, normal and Na(+)-free Ringer solutions and in the presence of bumetanide, chlorothiazide and ouabain. The observed volume changes following increases in extracellular tonicity were compared with microelectrode measurements of steady-state resting potentials (E(m)). Fibres in isotonic Cl(-)-free, normal and Na(+)-free Ringer solutions showed similar E(m) values consistent with previously reported permeability ratios P(Na)/P(K)(0.03-0.05) and P(Cl)/P(K) ( approximately 2.0) and intracellular [Na(+)], [K(+)] and [Cl(-)]. Increased extracellular osmolarities produced hyperpolarizing shifts in E(m) in fibres studied in Cl(-)-free Ringer solution consistent with the Goldman-Hodgkin-Katz (GHK) equation. In contrast, fibres exposed to hypertonic Ringer solutions of normal ionic composition showed no such E(m) shifts, suggesting a Cl(-)-dependent stabilization of membrane potential. This stabilization of E(m) was abolished by withdrawing extracellular Na(+) or by the combined presence of the Na(+)-Cl(-) cotransporter (NCC) inhibitor chlorothiazide (10 microM) and the Na(+)-K(+)-2Cl(-) cotransporter (NKCC) inhibitor bumetanide (10 microM), or the Na(+)-K(+)-ATPase inhibitor ouabain (1 or 10 microM) during alterations in extracellular osmolarity. Application of such agents after such increases in tonicity only produced a hyperpolarization after a time delay, as expected for passive Cl(-) equilibration. These findings suggest a model that implicates the NCC and/or NKCC in fluxes that maintain [Cl(-)](i) above its electrochemical equilibrium. Such splinting of [Cl(-)](i) in combination with the high P(Cl)/P(K) of skeletal muscle stabilizes E(m) despite volume changes produced by extracellular hypertonicity, but at the expense of a cellular capacity for regulatory volume increases (RVIs). In situations where P(Cl)/P(K) is low, the same co-transporters would instead permit RVIs but at the expense of a capacity to stabilize E(m).

Animals↗
PubMed1977

Role of the membrane potential in serum-stimulated uptake of amino acid in a diploid human fibroblast.

The Na+-dependent accumulation of alpha-aminoisobutyric acid (AIB), measured in normal growing and quiescent (serum-deprived) HSWP cells (human diploid fibroblast), was found to be twofold higher (AIB/in/AIBout = 20-25) under the normal growing conditions. Serum stimulation of quiescent cells increases their AIB concentrating capacity by approximately 70% within 1 hr. These observations suggest that the driving forces for AIB accumulation may be reversibly influenced by the serum concentration of the growth medium. Addition of valinomycin (Val) to cells preequilibrated with AIB causes an enhanced accumulation of AIB, suggesting that the membrane potential can serve as a driving force for AIB accumulation. After preequilibration with AIB in 6 mM K+, transfer to 94 mM K+ with Val results in a marked and rapid net loss of AIB. The effect of Val on the accumulation of AIB is greatest in quiescent cells, with the intracellular AIB concentrations reaching those seen both in Val-stimulated normal cells and in Val-stimulated serum-stimulated cells. By adjusting [K+]0, in the presence of Val, the membrane potential of growing cells can be matched to that of quiescent cells or vice versa. When this is done, the two accumulate AIB to the same extent. Hence the AIB accumulating capacity is characteristic of the membrane potential rather than of the growth state. In summary, these data suggest that the accumulation of AIB in HSWP cells is influenced by changes in membrane potential and that a serum-associated membrane hyperpolarization could be responsible for the increased capacity for AIB accumulation in serum-stimulated cells.

Aminoisobutyric Acids↗
PubMed1988

The dependence of motoneurone membrane potential on extracellular ion concentrations studied in isolated rat spinal cord.

1. Intracellular recordings from ninety-nine motoneurones have been made in an in vitro hemisected spinal cord preparation. Their mean resting membrane potential in normal artificial cerebrospinal fluid (CSF) was -71 +/- 0.5 mV (+/- S.E.M.). The mean amplitude of the action potential was 84.0 +/- 1.4 mV (n = 50), and the mean input conductance was 101 +/- 7 nS (n = 49). 2. Both membrane potential and input conductance were sensitive to changes in [K+]o, [Na+]o, [Cl-]o and [Ca2+]o. 3. Replacement of extracellular Ca2+ by Mn2+ resulted in less than 1 mV hyperpolarization and a decrease in input conductance from 102 +/- 7 to 93 +/- 6 nS (n = 15). 4. At high [K+]o (greater than 10 mM) the membrane potential followed the potential predicted by the Nernst equation for K+ ions with a slope of 58 mV per 10-fold change in [K+]o. At low [K+]o (less than 10 mM) there was significant deviation from K+ equilibrium potential (EK). 5. [K+]i was found to be 106 mM when estimated from the reversal potential of the after-hyperpolarization of the antidromic action potential. 6. The reversal potential of the recurrent inhibitory postsynaptic potential (IPSP) in normal CSF was used to calculate [Cl-]i. This was 6.6 mM, which is less than would be expected if Cl- was passively distributed, indicating the presence of an outwardly directed Cl- pump. 7. Decreasing [Cl-]o from control (134 mM) to 4 mM resulted in a depolarization of 6.9 +/- 0.9 mV and a decrease in input conductance from 102 +/- 5 to 90 +/- 5 nS (n = 14) in 3 mM [K+]o. 8. Decreasing [Na+]o from 156 to 26 mM by substitution with choline resulted in a 6.2 +/- 0.5 mV hyperpolarization and a decrease in input conductance from from 102 +/- 4 to 76 +/- 4 nS (n = 5) in 3 mM [K+]o. 9. The input conductances for Na+, Cl- and K+ at the resting potential were calculated. After allowing for a microelectrode leak conductance, the relative input conductances were gNa/gK = 0.13 and gCl/gK = 0.25.

Action Potentials↗
PubMed1992

Determination of transmembrane pH gradients and membrane potentials in liposomes.

Techniques for determining large transbilayer pH gradients (delta pH) and membrane potentials (delta psi) induced in response to delta pH in large unilamellar vesicle liposomal systems by measuring the transbilayer redistribution of radiolabeled compounds have been examined. For liposomes with acidic interiors, it is shown that protocols using radiolabeled methylamine in conjunction with gel filtration procedures to remove untrapped methylamine provide accurate measures of delta pH in most situations. Exceptions include gel state lipid systems, where transbilayer equilibration processes are slow, and situations where the interior buffering capacity is limited. These problems can be circumvented by incubation at elevated temperatures and by using probes with higher specific activities, respectively. Determination of delta pH in vesicles with a basic interior using weak acid probes such as radiolabeled acetate in conjunction with gel filtration was found to be less reliable, and an alternative equilibrium centrifugation protocol is described. In the case of determinations of the membrane potentials induced in response to these pH gradients, probes such as tetraphenylphosphonium and thiocyanate provide relatively accurate measures of the delta psi induced. It is shown that the maximum transmembrane pH gradient that can be stably maintained by an egg phosphatidylcholine-cholesterol 100-nm-diam large unilamellar vesicle is approximately 3.7 units, corresponding to an induced delta psi of 220 mV or transbilayer electrical field of 5 x 10(5) V/cm.

Biophysical Phenomena↗
PubMed2001

Subthreshold membrane potential oscillations of type A neurons in injured DRG.

An abundance of subthreshold membrane potential oscillations (SMPOs) at resting potential was observed in the neurons of chronically compressed dorsal root ganglia (DRG) using intracellular recording in vivo. Out of 386 neurons, 63 type A neurons displayed SMPOs. Three types of SMPOs were distinguished based on their characterizations of oscillation: (1) A regular pattern of SMPO emerged consistently with a mean frequency of 86 Hz and mean amplitudes of 3.3 mV. (2) A spindle-like pattern of SMPO was denominated by a spindle alteration of its amplitude. (3) An irregular pattern of SMPO had no rule on its change of amplitude and frequency. Compared with normal DRG neurons and injured DRG neurons but without SMPO, the injured DRG neurons with SMPO had the lowest spike rheobase, in accordance with the detection of spike accommodation. No significant differences among the three groups can be found in either membrane potential or input resistance. Further observation showed that the spontaneous discharge of hyperexcitable neurons usually occurred on the depolarizing phase of oscillations. In addition, the regular pattern of SMPO was based on the period and integer multiple patterns of spontaneous discharges. The spindle-like pattern of SMPO contributed to spontaneous bursting discharge. The irregular pattern of SMPO had a striking relation with irregular spontaneous discharge. The results show that neurons with SMPO in injured DRG have a higher excitability than those without SMPO, and that the SMPO underlie the patterns of spontaneous discharges, suggesting that SMPO is the basic electrophysiological change of hyperexcitable neurons.

Animals↗
PubMed2002

Changes in membrane potential induced by compound 48/80 in the peritoneal mast cells of rats.

The changes in membrane potential induced by compound 48/80 were studied using rat peritoneal mast cells. The mean resting membrane potential of rat mast cells was -12.3 +/- 0.7 mM. When compound 48/80 was added to the mast cells, the cells were degranulated approximately 120 sec after the addition of the drug, after which immediate depolarization occurred. Degranulation of mast cells was not observed, even under the depolarization or hyperpolarization conditions caused by the replacement of a high K+ medium or the removal of K+ from the medium, respectively. Under both conditions, when compound 48/80 was added to the mast cells, degranulation was observed. Abrupt and marked depolarization was induced 30-60 sec after compound 48/80 was added. In addition, repolarization followed by gradual depolarization was observed without degranulation in mast cells treated with cytochalasin D after the addition of compound 48/80. These results suggest that the mast cells were depolarized by compound 48/80 independently of degranulation. It is also feasible that the gradual depolarization and repolarization induced by compound 48/80 in mast cells pretreated with cytochalasin D participated in the extracellular Na+ and Na+/K(+)-pump, respectively.

Animals↗
PubMed2006

Role of membrane potential on artificial transformation of E. coli with plasmid DNA.

The standard method of transformation of Escherichea coli with plasmid DNA involves two important steps: cells are first suspended in 100mM CaCl(2) at 0 degrees C (in which DNA is added), followed by the administration of a heat-pulse from 0 to 42 degrees C for 90s [Cohen, S., Chang, A., Hsu, L., 1972. Nonchromosomal antibiotic resistance in bacteria. Proc. Natl. Acad. Sci. U.S.A., 69, 2110-2114]. The first step makes the cells competent for uptake of DNA and the second step is believed to facilitate the DNA entry into the cells by an unknown mechanism. In this study, the measure of membrane potential of the intact competent cells, at different steps of transformation process, either by the method of spectrofluorimetry or that of flow cytometry, indicates that the heat-pulse step (0-->42 degrees C) heavily decreases the membrane potential. A subsequent cold shock (42-->0 degrees C) raises the potential further to its original value. Moreover, the efficiency of transformation of E. coli XL1 Blue cells with plasmid pUC19 DNA remains unaltered when the heat-pulse step is replaced by the incubation of the DNA-adsorbed competent cells with 10 microM carbonyl cyanide m-chlorophenyl hydrazone (CCCP) for 90s at 0 degrees C. Since the CCCP, a well-known protonophore, reduces membrane potential by dissipating the proton-motive-force (PMF) across E. coli plasma membrane, our experimental results suggest that the heat-pulse step of the standard transformation procedure facilitates DNA entry into the cells by lowering the membrane potential.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMed2004

Effect of membrane potential depolarization on the organization of the actin cytoskeleton of eye epithelia. The role of adherens junctions.

We have previously determined that the depolarization of the plasma membrane potential of confluent bovine corneal endothelial cells in culture, provokes a characteristic reorganization of the actin cytoskeleton. The purposes of the present work are to investigate whether similar responses are exhibited by other epithelia, irrespectively of their specific functions and embryonic origin, and to test the hypothesis that the cytoskeletal reorganization induced by membrane depolarization requires of a well-organized circumferential actin disposition in order to take place. For this, we have performed studies on three different cultured epithelia of the eye: bovine corneal endothelium, bovine retinal pigment epithelium and cellular lines of murine lens epithelium. For all of these cells, we explored the effects of plasma membrane depolarization, achieved via the incorporation of gramicidin D to the bathing media or by the replacement of extracellular sodium chloride by potassium gluconate, on the cadherin and actin distribution. The membrane potential changes were monitored by fluorescence microscopy using oxonol V; fluorescent probes were also used for F-actin and cadherin. Detergent extraction and Western blot analysis were employed to reveal the relative amount of cadherin attached to the cytoskeleton. The main findings of this study are that different confluent cultured epithelia exhibiting a well-defined circumferential pattern of actin distribution respond to plasma membrane depolarization by similar modifications in the actin cystoskeleton to those reported for bovine corneal endothelial cells. On the other hand, epithelia that do not exhibit such actin pattern in confluence, as well as non-confluent monolayers, do not display noticeable actin modifications in response to the depolarizing procedures. While in the former cells, cadherin is predominantly located at the lateral membrane domain, the cells that do not respond to membrane depolarization mainly display their cadherin in the intracellular compartment. We suggest that the typical peripheral disposition of actin, associated to well-established epithelial-type adherens junctions (i.e. zonula adherens), is a pre-requisite for the cytoskeletal organizational modifications exhibited by epithelial cells in response to the depolarization of the plasma membrane potential.

Actins↗
PubMed1991

Chloride and membrane potential dependence of sodium ion-proline symport.

Proline accumulation by renal proximal tubule brush border membrane vesicles is Na+ dependent, but little is known about the role of anions or membrane potential on proline uptake. Recent studies in a variety of transport systems, including rat renal brush border membrane vesicles, indicate that halide anions chloride (Cl-) and bromide (Br-) are essential for glycine, beta-alanine, gamma-aminobutyric acid, and taurine uptake, so the possibility that Na(+)-proline symport is Cl- dependent was explored. Also, the role of membrane potential on transport was assessed by determining the effect of external anions with different membrane permeabilities. The ratio of initial rate Cl- stimulated to thiocyanate (SCN)(-)-stimulated uptake values serves to measure Cl- dependence. The initial rate of proline uptake to equilibrium value was 3.11 +/- 0.5 (SE) in the presence of Cl- versus SCN-. The ratio for D-glucose, whose uptake is governed only by electrogenic status of the membrane, was 0.61 +/- 0.47 (P less than 0.001 versus proline). In another series of experiments, uptake values for various anions as a percent of equilibrium (I/E x 100) were: SCN-, 84.9 +/- 10.9; NO3, 49.9 +/- 11.0; SO4(2-), 27.3 +/- 4.4; F-, 68.5 +/- 18.3; Cl-, 164.1 +/- 44.6; Br-, 150.6 +/- 30.2; I-, 56.7 +/- 13.5. The stoichiometry of uptake by Hill plot analysis of proline uptake in the presence of varying concentrations of Na+ (0 to 100 mM) and Cl- (0 to 100 mM) was 2Na+:1Cl-:1 proline.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Transport Systems, Neutral↗
PubMed1985

The effect of Na+ and Cl- removal and of loop diuretics on acetylcholine-evoked membrane potential changes in mouse lacrimal acinar cells.

Intracellular micro-electrode recordings were made from acinar units in mouse lacrimal gland segments superfused with physiological saline solutions. Two micro-electrodes were used: one for recording the membrane potential and the other for current injection. A third extracellular micropipette was used for local ionophoretic acetylcholine (ACh) application. The ACh-evoked membrane potential change was recorded at the spontaneous resting potential and after the resting potential had been increased or decreased by direct current injection. The membrane potential at which ACh did not evoke any change in potential (null potential, reversal potential) (EACh) was determined. EACh was about -53 mV under normal ionic conditions. When all Cl- in the superfusion fluid was replaced by NO3- or all Na+ replaced by N-methyl-D-glucamine+ (NMDG+) or Tris+, EACh was shifted to more negative values. During exposure to Cl(-)-free NO3- solution or Na+-free NMDG+ solution EACh was about -72 mV. These effects on EACh were fully reversible. Inclusion of the loop diuretics piretanide (2 x 10(-4) M) or furosemide (10(-3) M) also shifted EACh towards more negative values. In these cases EACh was the same as during exposure to Na+-free Tris+ solution with a value of about -62 mV. Replacement of extracellular Cl- by Br- had no effect on EACh whereas replacement of Na+ by Li+ shifted Each towards less negative values.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Morphological changes and membrane potential of human granulocytes under influence of chemotactic peptide and/or echo-virus, type 9.

The membrane potential, Em, of human granulocytes (PMNs), was recorded using glass microelectrodes. The membrane potential Em exhibited potential fluctuations accompanied by characteristic changes of cell shape. The periodic potential fluctuations (7-s, 70-s, and 260-s periodicities) ascertained by the autocorrelation technique, suggested the existence of an internal clock. The chemoattractant f-Met-Leu-Phe (FMLP) had no influence on the periodicities, whereas the amplitudes of the fluctuations were increased by it. Treatment of PMNs with Echo 9 virus also resulted in hyperpolarization. The 70-s periodicity disappeared under virus treatment indicating a virus-induced change of the internal program and loss of chemotactic activity.

Cell Transformation, Viral↗
PubMed2001

Contribution of the hyperpolarization-activated current (I(h)) to membrane potential and GABA release in hippocampal interneurons.

Intrinsic GABAergic interneurons provide inhibitory input to the principal neurons of the hippocampus. The majority of interneurons located in stratum oriens (s.o.) of the CA1 region express the hyperpolarization-activated cation current known as I(h). In an effort to elucidate the role of this current in regulating the baseline excitability of these neurons and its participation in the regulation of the release of GABA onto CA1 pyramidal neurons, we utilized whole cell electrophysiological recordings from both populations of cells. In voltage-clamp experiments, hyperpolarization of the interneuron membrane initiated a large inward current with an estimated activation threshold of 51.6 +/- 7.6 mV and a half-maximal voltage of -73.0 +/- 7.0 mV. This current was blocked by bath application of the I(h) inhibitors ZD 7288 (50 microM) or cesium (2 mM). Current-clamp experiments at the interneuron resting membrane potential (-61.3 +/- 1.2 mV) revealed a significant hyperpolarization, a decrease in the rate of spontaneous action potential discharge, an increase in the cellular input resistance, and the elimination of rebound afterdepolarizations during blockade of I(h) with ZD 7288 (50 microM). The hyperpolarizing effect of ZD 7288 was also substantially larger in interneurons clamped near -80 mV using current injection through the pipette. In addition to neurons exhibiting I(h), recordings were obtained from a small population of s.o. interneurons that did not exhibit this current. These cells demonstrated resting membrane potentials that were significantly more negative (-73.6 +/- 5.5 mV) than those observed in neurons expressing I(h), suggesting that this current contributes to more depolarized membrane potentials in these cells. Recordings from postsynaptic pyramidal neurons demonstrated that blockade of I(h) with ZD 7288 caused a substantial reduction (approximately 43%) in the frequency of spontaneous action potential-dependent inhibitory postsynaptic currents (IPSCs), without altering their average amplitude. However, miniature action-potential-independent IPSC frequency, amplitude, and decay kinetics were unaltered by ZD 7288. These data suggest that I(h) is active at the resting membrane potential in s.o. interneurons and as a result contributes to the spontaneous activity of these cells and to the tonic inhibition of CA1 pyramidal neurons in the hippocampus.

Animals↗
PubMed1995

Effect of 5-hydroxytryptamine on the membrane potential of endothelial and smooth muscle cells in the pig coronary artery.

1. Many endothelium-dependent vasodilators hyperpolarize the endothelial cells in blood vessels. It is not known whether these hyperpolarizations are linked to nitric oxide synthesis or to an endothelium-derived hyperpolarizing phenomenon, since most of the vasodilators release both factors. In this context, we first verified that the endothelium-dependent relaxations induced by 5-hydroxytryptamine (5-HT) on pig coronary arteries are due only to the activation of the nitric oxide pathway. Then we studied the effects of 5-HT on membrane potential of endothelial and smooth muscle cells. 2. In the absence of endothelium, 5-HT caused a concentration-dependent contraction of coronary artery strips. No change of the smooth muscle cell membrane potential was observed during contraction to 1 microM 5-HT. 3. In the presence of 1 microM ketanserin to suppress the contractile effect of 5-HT, 5-HT induced concentration-dependent relaxation of endothelium-intact strips precontracted by 10 microM prostaglandin F2 alpha (PGF2 alpha). These relaxations were suppressed by 1 microM NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, showing that they were produced predominantly by nitric oxide. 4. In the presence of 1 microM ketanserin, 1 microM 5-HT did not change the smooth muscle cell membrane potential of strips precontracted by either 10 microM PGF2 alpha or by 10 microM acetylcholine (ACh). In the same conditions, 1 microM 5-HT caused a weak 2.6 +/- 0.4 mV hyperpolarization, of the endothelial cells. 5. In conclusion, the fact that 5-HT did not change the membrane potential of smooth muscle cells and only weakly hyperpolarized the endothelial cells during relaxations, suggests that in both cell types no electrical events accompany activation of the nitric oxide pathway. This is in contrast to the hyperpolarizations observed in endothelial and smooth muscle cells when the endothelium-derived hyperpolarization factor (EDHF) pathway is activated.

Animals↗