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At least 127 records · Page 7Linked to original sources
PubMed1984

An analysis of the rate-dependent action of lidoflazine in mammalian sino-atrial node and Purkinje fibres.

Lidoflazine is an anti-anginal drug whose beneficial effect is to reduce the heart rate increment on exercise. Micro-electrode recording was performed in the spontaneously-beating, isolated guinea-pig sino-atrial node. It was shown that low concentrations (less than 5 X 10(-6) M) of lidoflazine alone did not alter action potential configuration or beating frequency. However, the drug reduced the spontaneous rate and the slope of the diastolic depolarization in the presence of catecholamine. This effect of lidoflazine was more pronounced at higher catecholamine concentrations. The action of lidoflazine on the hyperpolarization-activated current if was studied using a 2-micro-electrode voltage-clamp technique on shortened sheep Purkinje fibres. The activation curve for if was not affected by the drug. The slope of the fully-activated current-voltage relation was reduced by a mean of 20.1% on exposure to 5 X 10(-6) M lidoflazine. Using a computer model of Purkinje fibre action potentials, the observed reduction in maximal if conductance was shown to account quantitatively for the effects of lidoflazine. It is proposed that lidoflazine slows the heart by reducing the conductance of the if channel. This may be brought about by a fall in intracellular calcium concentration.

Action Potentials↗
PubMed1998

Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models.

Mechanoelectric coupling in the heart is well documented and has been suggested as a cause of arrhythmia. One hypothesized mechanism for the stretch sensitivity of cardiac muscle is the presence of stretch-activated channels (SACs). This study uses modeling to explore the influence of SACs on cardiac resting potential, excitation threshold, and action potential in the context of arrhythmia. We added a putative SAC, modeled as a linear, time-independent conductance with reversal potential of -20 or -50 mV, to guinea pig and frog ventricular membrane models. Increased stretch conductance led to resting potential depolarization, a decreased excitation threshold, altered action potential duration, and, under certain conditions, early afterdepolarizations. We conclude that stretch increases cellular excitability, making the heart prone to ectopic activity. Regional effects of stretch on action potential duration can vary and are influenced by factors such as the SAC reversal potential, ionic conditions, and baseline currents, all of which may lead to an increased dispersion of refractoriness throughout the heart and therefore an increased risk of arrhythmia.

Action Potentials↗
PubMed1984

Regional distribution of action potential abnormalities induced by subacute right ventricular pressure overload.

Right ventricular pressure overload of 3 days' duration was established in cats by banding of the pulmonary artery. To characterize the regional distribution of the resulting electrophysiologic changes, the right ventricular free wall, adjacent pulmonary outflow tract and septum were mounted in tissue bath and examined by conventional microelectrode techniques. Abnormal action potentials, identified by a negative shift of the voltage level of phase 2 with a corresponding accentuation of phase 1, were recorded from sites contiguous to the tricuspid valve and pulmonary outflow tract and in limited adjacent areas. No abnormal action potentials were recorded on the septal surface, apical end of the free wall, or at any right ventricular location in normal or sham-operated cats. Abnormal potentials could be recorded from sites sampled 5 cell layers deep in the endocardium. The number and extent of distribution of cells demonstrating altered action potentials correlated best with increased right ventricular wet weight at time of sacrifice. Abnormal cells responded to epinephrine or elevated extracellular calcium by a shift in plateau voltage towards zero and by an increase in action potential duration prior to usual plateau shortening. Responsiveness of these cells to agents which influence slow inward current suggests pressure overload-induced changes in the cell membrane that limit or otherwise affect availability of calcium. Regional distribution of plateau potential abnormalities may reflect differential physical stress within the myocardium provoked by sudden pressure overload.

Action Potentials↗
PubMed1997

Toxicity of cadmium in human trophoblast cells (JAr choriocarcinoma): role of calmodulin and the calmodulin inhibitor, zaldaride maleate.

Cadmium (Cd), the heavy metal, is toxic to the placenta. The objectives of this study were to determine if Cd toxicity is due to inhibition of placental or trophoblast cell proliferation through interactions with the intracellular calcium binding protein, calmodulin (CaM). Cd can replace calcium and thus interfere with CaM's function. Also, CaM inhibitors reverse selected toxic effects of Cd. The CaM inhibitor, zaldaride maleate, was used to determine if Cd inhibits trophoblast cell proliferation through interactions with CaM. JAr choriocarcinoma cells, a neoplastic trophoblast cell line which is similar to early human trophoblast cells, were selected to study this question. Cd (20 and 40 microM) inhibits JAr cell proliferation, as measured by cell number and BrdU incorporation. Zaldaride (10 and 20 microM) inhibits proliferation to a lesser extent; 100 microM is lethal. To determine if zaldaride alters actions of Cd, zaldaride and Cd are added simultaneously. Zaldaride (20 microM) and Cd (20 microM) together inhibit proliferation less than Cd alone, thus partially protecting cells. Metallothionein is induced in cells exposed to Cd, while zaldaride does not cause induction of this cellular defense mechanism protein. To determine if Cd inhibits proliferation through alterations of cell cycle, JAr cells enriched for G0/G1 phase were exposed to 20 microM Cd, 20 microM zaldaride, or 20 microM Cd plus 20 microM zaldaride for 24 hr. Cells remain in G0/G1 following Cd exposure; cells treated with 20 microM zaldaride progress through S phase and into G2. Zaldaride and Cd together allow JAr cells to leave G1 and enter S phase, partially relieving the cycle block produced by Cd. This study demonstrates a role for calmodulin in mediating the toxicity of Cd in trophoblast cell proliferation.

Antidiarrheals↗
PubMed1990

Suppression of repolarization-related arrhythmias in vitro and in vivo by low-dose potassium channel activators.

Marked prolongation of cardiac action potentials and of QT intervals has been associated with early afterdepolarizations and triggered activity in vitro and with ventricular tachycardia in vivo. Because the antihypertensive potassium channel activators pinacidil and cromakalim are known to accelerate repolarization in cardiac tissues, we performed in vitro and in vivo experiments to test the hypothesis that these agents would block the arrhythmogenic effects of delayed repolarization. Early afterdepolarizations and triggered activity were elicited in canine cardiac Purkinje fibers driven at cycle lengths of 4 seconds or more (K0, 2.7 mM) during superfusion with quinidine, cesium, or sematilide, a methylsulfonylamino parasubstituted analogue of procainamide with class III antiarrhythmic activity. The potassium channel activators invariably (17 of 17) abolished this form of abnormal automaticity. This effect was observed at low concentrations that did not alter action potential characteristics at shorter cycle lengths. Intravenous Cs+ (total dose, 4.5 mM/kg) was used to produce ventricular arrhythmias in anesthetized rabbits randomly pretreated in a double-blind fashion with either low-dose pinacidil (0.2 mg/kg) or vehicle. Pinacidil pretreatment resulted in significantly fewer total ventricular ectopic beats (168 +/- 157 versus 582 +/- 448, p less than 0.005) and episodes of ventricular tachycardia (four of nine versus nine of nine, p = 0.057). At this dose, pinacidil did not alter mean blood pressure before Cs+ and maximal hypertensive response after Cs+. In summary, the potassium channel activators pinacidil and cromakalim suppressed triggered activity related to prolonged repolarization at concentrations that did not affect action potential characteristics at normal rates in vitro; pinacidil blunted arrhythmias produced by cesium administration in vivo without lowering blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

[Catecholamines in the mechanism of the cardionecrotic action of acetaldehyde].

Administration of acetaldehyde to rats by inhalation or intraperitoneally (in repeated doses) provokes an emergence of micronecroses in the myocardium. Administration of acetaldehyde in a dose causing no injury to the myocytes potentiates the cardionecrotic action of adrenalin. Pretreatment with L-DOPA potentiates while that of L-alpha-methyl-DOPA or alpha-methyl-p-tyrosine averts the necrosogenous action of acetaldehyde. Under isolated heart perfusion, acetaldehyde administered in the concentrations that exceeded 2-fold and more those in the blood in experiments in vivo had no necrosogenous action. The degree of the adrenalin-induced lesions of the isolated myocardium remained unchanged in the presence of acetaldehyde. It is assumed that the cardionecrotic effect of acetaldehyde is mediated by catecholamines and is effected by stimulation of biogenic amine release from neurons and chromaffin tissue, and is not linked with direct acetaldehyde effect on the realization of the alterative action of catecholamines.

Acetaldehyde↗
PubMedDate not supplied

[Pharmacologic complications of the unequal reactivity of constituent elements of the myocardium to the parasympathetic system].

Pharmacological consequences of the unequal reactivity of the myocardial different parts to parasympathic system. The effects of acetylcholine on the various levels of cardiac automatism are studied on open chest dogs with extracorporeal circulation. This drug depresses the sinus node, and more specially the atrio-ventricular node (AV node), but does not alter the His bundle and the Purkinje fibers activity. The sensitivity of the intra-cardiac conduction to acetylcholine also depends upon the considered level of conduction: measured with a bipolar electrode situated upon the His bundle, this one is lowered electively in the atrio-ventricular part. So, the A, V. node can be considered as the elective place of action of acetylcholine on the double point of view of automatism and conduction. Drugs modifying the vagal tonus see their action altered, either in a plus way (antiarrhythmic agents), either in a minus way (cardiac glycosides, halogenated hydrocarbons).

Acetylcholine↗
PubMed1992

Audit of compliance with antenatal protocols.

OBJECTIVE: To assess the implementation of action protocols dictated by antenatal risk factors noted at the initial (booking) antenatal visit. DESIGN: Retrospective study of 2000 women delivered between 1 March 1990 and 29 March 1991. SETTING: Maternity department of a district general hospital supporting a multiethnic population in inner London. MAIN OUTCOME MEASURES: Comparison of clinical actions performed against those dictated by the department's protocols. Analysis according to clinical importance, gestation at booking, maternal age, parity, birth order, ethnic origin, and certainty of gestational age. RESULTS: Interobserver agreement between the two auditors was good (kappa statistic for risk factors detected, 0.78; for actions generated, 0.80). Of the 15,658 actions dictated by department protocols, 3673 (23.5%) were actually performed by the clinicians. The 63 combinations of risk factors and actions believed by consultants to be of particular clinical importance had an action rate of 28.3% compared with 18.6% for those considered less important (p < 0.001). Mothers who first visited the hospital antenatal clinic at or before 24 weeks' gestation had 25.2% of relevant protocols fulfilled (p < 0.001). Compliance was significantly improved in women aged 36 or over (32.4%), black women (24.9%), and cases of uncertain gestation (24.5%). Parity and birth order were not associated with an altered action rate. Ethnic origin deemed as "other" (than white, black, Asian, or oriental) or "unknown" was associated with poor compliance (19.3%). CONCLUSIONS: Compliance to a set of agreed protocols was poor even though a computer system was available and a protocol manual had been distributed. Protocols were more likely to be implemented in women who booked early and in some groups of women deemed at high risk including older mothers, black women, and those denoted as having uncertain gestational age.

Clinical Protocols↗
PubMed1980

Some mechanisms underlying actions of ketamine on electromechanical coupling in skeletal muscle.

The effects on excitation contraction coupling (ECC) of ketamine (a dissociative general anesthetic) were investigated using the sartorius muscle of the frog. Extracellular studies revealed that ketamine depressed action potential production in a concentration-dependent manner. Ketamine decreased both the conduction velocity and the compound action potential while concomitantly increasing the threshold current. Intracellular studies showed that ketamine caused a slight non-significant decrease in the membrane potential and also decreased the threshold potential (mechanical threshold). Ketamine (1.5 X 10(-4) M and 3.0 X 10(-4) M) initially potentiated and then blocked the twitch response elicited by direct muscle stimulation. Both of these effects were statistically different from control values. These findings suggest that ketamine alters action potential production in frog skeletal muscle. This property of ketamine contributes in part to the disruption of ECC observed with this drug. The results suggest the ketamine probably interferes with calcium binding, its release and/or its fluxes which may contribute to the intial potentiation and subsequent depression of twitch tension.

Animals↗
PubMed1991

Mode of action of the new quinolones: new data.

New details of the molecular interactions of quinolones with their target DNA gyrase and DNA have come from the nucleotide sequences of the gyrA genes from resistant mutants of Escherichia coli and wild-type strains of other bacteria and studies of gyrase A tryptic fragments, all suggesting the importance of an amino-terminal domain in quinolone action. Alterations in DNA supertwisting were also associated with altered quinolone susceptibility, possibly by indirect effects on DNA gyrase expression. Specific binding of relevant concentrations of norfloxacin to a complex of DNA gyrase and DNA in the presence of ATP, the cooperativity of DNA binding, and the crystalline structure of nalidixic acid have led to a model in which quinolones bind cooperatively to a pocket of single-strand DNA created by DNA gyrase. Quinolones vary in their relative activity against DNA gyrase and its eukaryotic homolog topoisomerase II, and in some assays increased action against the eukaryotic enzyme was associated with genotoxicity. Inhibition of bacterial DNA synthesis by quinolones may correlate with MICs in some species, but comparisons of drug accumulation and inhibition of DNA synthesis in permeabilized cells among species have been difficult to interpret. The specific factors necessary for bacterial killing by quinolones in addition to interaction with DNA gyrase have remained elusive, but include oxygen and new protein synthesis. The coordinate expression of the SOS proteins appears not to be necessary for quinolone lethality. Two independent mutants with selective reduced killing by quinolones and beta-lactams indicate overlap in the pathways of bactericidal activity of these classes of agents with distinct targets.

4-Quinolones↗
PubMed2001

Neurosteroids in learning and memory processes.

The discovery that neurosteroids could be synthesized de novo in the brain independent from the periphery and display neuronal actions led to great enthusiasm for the study of their physiological role. Pharmacological studies suggest that neurosteroids may be involved in several physiological processes, such as learning and memory. This chapter summarizes the effects of the administration of neurosteroids on learning and memory capabilities in rodents and in models of amnesia. We address the central mechanisms involved in mediating the modulation of learning and memory processes by neurosteroids. In this regard, the neurosteroid-modulated neurotransmitter systems, such as gamma-aminobutyric acid type A, N-methyl-D-aspartate, and cholinergic and sigma opioid systems, appear to be potential targets for the rapid memory alteration actions of neurosteroids. Moreover, given that some neurosteroids affect neuronal plasticity, this neuronal change could be involved in the long-term modulation of learning and memory processes. To understand the role of endogeneous neurosteroids in learning and memory processes, we present some physiological studies in rodents and humans. However, the latter do not successfully prove a role of endogenous neurosteroids in age-related memory impairments. Finally, we discuss the relative implication of a given neurosteroid vs its metabolites. For this question, a new approach using the quantitative determination of traces of neurosteroids by mass spectrometry seems to have potential for examining the role of each neurosteroid in discrete brain areas in learning and memory alterations, as observed during aging.

Animals↗
PubMed2003

Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart.

INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

Action Potentials↗
PubMed2002

Cholinergic interneuron characteristics and nicotinic properties in the striatum.

The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

Acetylcholine↗
PubMed1984

Effect of breathing pattern on esophageal pressure gradients in humans.

This study examines the hypothesis that respiratory muscle action alters regional pleural pressures. Seven normal volunteers were studied in the seated posture with three esophageal balloons positioned in the upper, middle, and lower esophagus. The intraesophageal pressure swings were recorded during natural breathing, enhanced rib cage, and enhanced diaphragmatic breathing. The pressures were also recorded at three frequencies ranging from 12 to 60 breaths/min. Data were processed with an ensemble average technique that largely removes cardiogenic artifact. During quiet natural breathing, the pressure swings in the lower esophagus were, on the average, 30% larger than the pressure swings in the upper esophagus but became nearly equal as the frequency increased to 60 breaths/min. Rib cage breathing nearly abolished the intraesophageal dynamic pressure differences, whereas abdominal breathing preserved the observed pressure difference even at 60 breaths/min. We concluded that muscle action can affect intrathoracic pressures in a regional way depending on the groups of muscles that are active. These results are discussed in terms of the topographical distribution of ventilation.

Adult↗
PubMed1991

Mechanisms of interaction among subinhibitory concentrations of antibiotics, human polymorphonuclear neutrophils, and gram-negative bacilli.

Our hypothesis was that pretreatment of bacteria with subinhibitory concentrations (sub-MICs) of antibiotics enhances the susceptibility of the organisms to killing by human polymorphonuclear neutrophils (PMNs). Our purpose was to study a variety of drugs with different mechanisms of action and to determine whether the mechanism and locus of action altered the sub-MIC effect. The following outcome measures were used: ingestion and killing of bacteria by PMNs, bacterial killing in the absence of phagosome formation, and binding requirements of the bacteria to PMNs. The antibiotics used were representative of a variety of classes, including beta-lactams (piperacillin and imipenem) and quinolones (ciprofloxacin). Bacterial uptake and killing were measured by using standard techniques, and results were analyzed by using the analysis-of-variance technique and Dunnett's t test. Pretreatment of Escherichia coli with all drugs showed significantly enhanced killing of bacteria by PMNs, which was independent of ingestion by the phagocytes. Even in the absence of phagosome formation, statistically significant killing persisted with piperacillin-pretreated bacteria but not with imipenem- or ciprofloxacin-pretreated organisms. The opsonization experiments showed that contact between bacteria and PMNs was necessary for killing to occur. The sub-MIC effect appears to be independent of the locus or mechanism of action of the antibiotic. It results in enhanced killing by PMNs which is independent of ingestion and also may persist even in the absence of phagosome formation. Killing is dependent upon specific contact between bacteria and an intact phagocyte.

Anti-Bacterial Agents↗
PubMed1992

Electrophysiologic actions of clofilium and lidocaine in ischemically injured canine epicardium.

The electrophysiologic actions of the Class III antiarrhythmic drug, clofilium, and the Class IB antiarrhythmic drug, lidocaine, were examined in ischemically injured canine epicardium, 4 days after coronary artery occlusion. Experiments were performed utilizing 1) composite electrode recordings from the intact heart in the anesthetized dog and 2) intracellular and extracellular recordings from superfused canine epicardium. In intact hearts, both clofilium (2 mg/kg i.v.) and lidocaine (6 mg/kg i.v.) increased refractoriness (188 +/- 16 to 331 +/- 39 and 288 +/- 18 msec, respectively, P less than .01), and produced tachycardia-dependent conduction disorders in ischemically injured epicardium. For both drugs, slowing the sinus heart rate with vagus nerve stimulation (32 +/- 6/min) returned activation delays to predrug values. Unlike lidocaine, clofilium failed to increase maximal activation delays in ischemically injured epicardium preceding conduction block (116 +/- 14 msec vs. 71 +/- 7 msec and 147 +/- 16 msec for clofilium and lidocaine, respectively, P less than .01 for both drugs). In superfused epicardium, both clofilium (3 x 10(-7) M) and lidocaine (4 mg/l) prolonged refractoriness in ischemically injured epicardium (175 +/- 16 predrug vs. 273 +/- 33 msec, P less than .01) and (181 +/- 3 predrug vs. 216 +/- 10 msec, P less than .01), respectively, whereas only lidocaine reduced Vmax and prolonged local conduction times in the same tissue. The results demonstrate that 1) lidocaine increases refractoriness in ischemically injured tissue via a decrease in Vmax and conduction velocity and 2) clofilium increases refractoriness in ischemically injured tissue without altering action potential duration, Vmax or conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Tolerance development to cadmium-induced alteration of drug action.

Cadmium administration potentiates the duration of hexobarbital-induced hypnosis and inhibits the rate of hepatic microsomal metabolism of this drug in the male rat. The threshold dose of cadmium required to produce these alterations in drug action is 0.84 mg Ck/kg. If subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) are administered prior to the 0.84 mg Cd/kg dose, the cadmium-induced alterations in drug action are no longer observed.

Animals↗
PubMed1995

Ethanol inhibits muscarinic receptor-stimulated phosphoinositide metabolism and calcium mobilization in rat primary cortical cultures.

In recent years, it has been hypothesized that muscarinic receptor-stimulated phosphoinositide (PI) metabolism may represent a relevant target for the developmental neurotoxicity of ethanol. Age-, brain region-, and receptor-specific inhibitory effects of ethanol on this system have been found, both in vitro and after in vivo administration. As a direct consequence of this action, alterations of calcium homeostasis would be expected, through alterations of inositol trisphosphate formation, which mediates intracellular calcium mobilization. In the present study, the effects of ethanol (50-500 mM) on carbachol-stimulated PI metabolism and free intracellular calcium levels were investigated in rat primary cortical cultures, by measuring release of inositol phosphates and utilizing the two calcium probes fluo-3 and indo-1 on an ACAS (Adherent Cell Analysis and Sorting) Laser Cytometer. Ethanol exerted a concentration-dependent inhibition of carbachol-stimulated PI metabolism. In addition, ethanol's inhibitory effect paralleled the temporal development of the muscarinic receptor signal transduction system, with the strongest inhibition (25-50%) occurring when maximal stimulation by carbachol occurs (days 5-7). Ethanol also exerted a concentration-dependent decrease in free intracellular calcium levels following carbachol stimulation. Both initial calcium spike amplitude, seen in all responsive cells, as well as the total number of cells responding to carbachol, were decreased by ethanol. The inhibitory effects of ethanol seemed dependent upon preincubation time, in that a longer preincubation (30 min) with the lowest dose (50 mM), showed almost the same decrease in responding cell number and reduction in spike amplitude in responding cells, as a shorter incubation (10 min) with the highest ethanol dose (500 mM). The specificity of the response to carbachol was demonstrated by blocking the response with 10 microM atropine. Moreover, experiments with carbachol in calcium-free buffer with 1 mM EGTA indicated that the initial calcium spike was due to intracellular calcium mobilization from intracellular stores. Since calcium is believed to play important roles in cell proliferation and differentiation, these results support the hypothesis that this intracellular signal-transduction pathway may be a target for ethanol, contributing to its developmental neurotoxicity.

Action Potentials↗