Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential

Summary Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization.The author gratefully acknowledges the generous financial support of the E.G. Schlieder Educational Foundation, the American Heart Association of Louisiana and the American Heart Association.     

Das Na-Transportsystem während der Erregungsprozesse am Ranvier-Knoten isolierter markhaltiger Nervenfasern

Summary (1) An attempt is made to interpret the action potential of medullated nerve fibres of the frog in terms of permeability changes to Na ions.(2) In keeping with a suggestion byHodgkin andHuxley, the following assumptions are made: (a) a carrier system is responsible for transporting Na ions across the nodal membrane; (b) in a resting fibre (high membrane potential) its transport capacity is small; (c) depolarization has a dual effect on the transport system, namely activation of carrier groups as a quick reaction and inactivation of the whole system as a slower reaction.(3) The following experimental observations are interpreted on the ground of these assumptions: threshold for depolarization, threshold for repolarization, absolute and relative refractory period, alteration of the action potential on application of a hypertonic (5%) NaCl solution.

---

---

Eine vorläufige Mitteilung erfolgte auf der Tagung des Schweiz. Vereins für Physiologie usw. in Fribourg 1956. Helv. physiol. Acta14, C35–36 (1956).     

Intracellular injection of cAMP and cGMP into snail neurones induces an increase in Na+-conductance

Injection of cAMP and more rarely cGMP into the neurones of the snail Helix pomatia induces an increase in membrane conductance, membrane depolarization and excitation. The effect is theophylline-dependent and has a reversal potential near -10mV.     

Time course of excitatory and inhibitory states of bulbar respiratory modulated neurons

Summary In respiratory modulated neurons of rabbits, vagally mediated inhibition is not bound to resting membrane potential oscillations. Latency of spinally evoked antidromical spike invasion, however, is shorter and threshold voltage is lower during the shift of membrane potential towards depolarization accompanying burst discharge.     

Contributions of cellular electrophysiology to the understanding of the electrocardiogram

The understanding of cardiac action potential and membrane currents has broadened the theoretical foundation and enhanced the clinical usefulness of the electrocardiogram. An improved understanding of the morphology of the electrocardiographic waveform has resulted from: correlations between Vmax of depolarization and QRS complex, plateau of the ventricular action potential and S-T segment, terminal repolarization and T-wave, from definitions of action potential differences responsible for the T-wave, and recordings of action potential alternans. Cellular electrophysiology has contributed to the understanding of certain mechanisms of cardiac standstill. Many disturbances of conduction and refractoriness associated with ventricular arrhythmias can be attributed to the following derangements at the cellular level: slowing of terminal repolarization, development of diastolic depolarization in fibers with stable resting membrane potential, after-depolarizations, currents of injury resulting from non-uniform polarization, increased dispersion of action potential durations, and co-existence of slow conduction and short premature action potentials.     

Intracellular injection of cAMP and cGMP into snail neurones induces an increase in Na+-conductance

Summary Injection of cAMP and more rarely cGMP into the neurones of the snailHelix pomatia induces an increase in membrane conductance, membrane depolarization and excitation. The effect is theophylline-dependent and has a reversal potential near — 10 mV.     

Contributions of cellular electrophysiology to the understanding of the electrocardiogram

Summary The understanding of cardiac action potential and membrane currents has broadened the theoretical foundation and enhanced the clinical usefulness of the electrocardiogram. An improved understanding of the morphology of the electrocardiographic waveform has resulted from: correlations between V_max of depolarization and QRS complex, plateau of the ventricular action potential and S-T segment, terminal repolarization and T-wave, from definitions of action potential differences responsible for the T-wave, and recordings of action potential alternans. Cellular electrophysiology has contributed to the understanding of certain mechanisms of cardiac standstill. Many disturbances of conduction and refractoriness associated with ventricular arrhythmias can be attributed to the following derangements at the cellular level: slowing of terminal repolarization, development of diastolic depolarization in fibers with stable resting membrane potential, afterdepolarizations, currents of injury resulting from non-uniform polarization, increased dispersion of action potential durations, and co-existence of slow conduction and short premature action potentials.     

Correlation between inhibition of stimulatory membrane repolarization and positive inotropic response caused by ouabain in rat heart]

During a stimulus train, the diastolic membrane potential of rat atria exhibits a depolarization phase followed by a slower repolarization phase which has been attributed to the activation of an electrogenic sodium pump (ATPase Na+, K+). This pump seems to be all the more active as stimulation frequency is higher. The parallel evolution of the sodium pump inhibition and a positive inotropic effect in response to ouabain perfusion, suggests that the enzymatic inhibition is directly involved in the development of the cardiotonic effect of digitalis.     

Consequences of acute ischemia for the electrical and mechanical function of the ventricular myocardium. A brief review

Reduction or interruption of the blood supply to the myocardium leads to marked disturbances of electrical and mechanical function within a few seconds. Electrical dysfunction is characterized by an initial depolarization of the resting membrane, and a decrease of the amplitude, the upstroke velocity and the duration of the action potential. Both depolarization and depression of the action potential are closely associated with intracellular metabolic acidosis. After this initial phase, electrical cell-to-cell uncoupling develops, probably as a consequence of increased cytosolic free [Ca++]. Mechanical dysfunction is characterized by a dissociation of the initial decrease of active force development from the subsequent ischemic contracture. Active force development in acute ischemia is inhibited by the accumulation of ischemic metabolic products (H+, inorganic phosphate (Pi), Mg++) but not by a marked decrease of [ATP]. The subsequent ischemic contracture is probably initiated by release of Ca++ from intracellular stores. This release causes rapid consumption of ATP and the development of rigor within 1-2 minutes.     

Interaction between bradykinin and voltage-sensitive sodium channels in myelinated nerve fibers

The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 microM) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of the membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by approximately 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.     

Voltage-gated sodium channel-associated proteins and alternative mechanisms of inactivation and block

Voltage-gated sodium channels mediate inward current of action potentials upon membrane depolarization of excitable cells. The initial transient sodium current is restricted to milliseconds through three distinct channel-inactivating and blocking mechanisms. All pore-forming alpha subunits of sodium channels possess structural elements mediating fast inactivation upon depolarization and recovery within milliseconds upon membrane repolarization. Accessory subunits modulate fast inactivation dynamics, but these proteins can also limit current by contributing distinct inactivation and blocking particles. A-type isoforms of fibroblast growth factor homologous factors (FHFs) bear a particle that induces long-term channel inactivation, while sodium channel subunit Navβ4 employs a blocking particle that rapidly dissociates upon membrane repolarization to generate resurgent current. Despite their different physiological functions, the FHF and Navβ4 particles have similarity in amino acid composition and mechanisms for docking within sodium channels. The three competing channel-inactivating and blocking processes functionally interact to regulate a neuron’s intrinsic excitability.     

High shortening velocity of isolated single arterial muscle cells

Surprisingly high shortening velocities (less than 200 msec contraction-relaxation cycles) were found in isolated vascular muscle cells cultured from rat or chick aorta. All of the small fraction cells with such quick contractions had membrane excitation by short duration spikes, rather than the slower graded depolarization of the other cells which produced 20-fold slower contractions.     

Identification of swelling-activated Cl<Superscript>-</Superscript> current in rabbit cardiac Purkinje cells

The presence and functional role of the swelling-activated Cl^- current (I_Cl(swell)) in rabbit cardiac Purkinje cells was examined using patch-clamp methodology. Extracellular hypotonicity (210 or 135 mOsm) activated an outwardly rectifying, time-independent current with a reversal potential close to the calculated Cl^- equilibrium potential (E_Cl). The magnitude of this current was related to tonicity of the superfusate. The current was blocked by 0.5 mM 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS). These features are comparable to those of I_Cl(swell) found in sinoatrial nodal, atrial, and ventricular myocytes. I_Cl(swell) activation at 210 and 135 mOsm depolarized the resting membrane potential with 6 and 10 mV and shortened the action potential by 18 and 33%, respectively. DIDS partially reversed I_Cl(swell)-induced action potential changes. We conclude that I_Cl(swell) is present in Purkinje cells and its activation leads to action potential shortening and resting membrane potential depolarization, both of which can promote the development of reentrant arrhythmias.Received 20 January 2004; received after revision 17 February 2004; accepted 25 February 2004     

Receptor potential of rat taste cell to potassium benzoate.

Rat taste cells responded to relatively low concentrations of K-benzoate with a hyperpolarization and to the high concentrations with a depolarization. During both responses the membrane resistance of a taste cell decreased. Depolarization elicited by application of a combination of 0.25 M NaCl and 0.05 M K-benzoate was smaller than that by the NaCl alone, indicating a depressant action of K-benzoate.     

An initial phasic depolarization exists in the receptor potential of taste cells.

When frog taste cells were stimulated by varying salts after adaptation to water, quinine or acetic acid, a phasic depolarization appeared initially in the receptor potential of taste cells. The initial transient depolarization may be related to the enhancement of an initial phasic response in the taste nerve.     

Receptor potential of rat taste cell to potassium benzoate

Summary Rat taste cells responded to relatively low concentrations of K-benzoate with a hyperpolarization and to the high concentrations with a depolarization. During both responses the membrane resistance of a taste cell decreased. Depolarization elicited by application of a combination of 0.25 M NaCl and 0.05 M K-benzoate was smaller than that by the NaCl alone, indicating a depressant action of K-benzoate.     

The effects of triaminopyrimidine on the short circuit current and transmembrane potentials of the isolated rat visceral yolk sac in vitro

Summary Intracellular potentials in the cells from 17.5-day old rat visceral yolk sacs were measured by a glass microelectrode. When penetrated from the maternal side, the cells have potentials of about 50.2±1.9 mV (inside negative) which were reduced by increasing the external K⁺ concentration and increased by removing Na⁺ ions from the bathing fluid. Triaminopyrimidine (TAP) which inhibited Na⁺ transport caused a dose-dependent depolarization of the cell membrane. The depolarization was dependent on the presence of extracellular Ca²⁺ ions. It is proposed that TAP may inhibit Na⁺ transport by increasing the intracellular concentration of calcium ions.This work was supported by the University of Hong Kong (grant number 335. 034.5105).Acknowledgment. Triaminopyrimidine was synthesized by Dr. Barbara Roth of the Wellcome Research Laboratories.     

External strontium and contractility in single giant muscle fibers of the barnacle

Summary Isometric tension and membrane potential in response to electrical stimulation have been studied on single giant muscle fibers of the barnacle upon replacement of external calcium with strontium. Under these conditions, the membrane response showed after the normal peak depolarization, a plateau phase lasting 3–7 sec before repolarization took place, while the force of contraction showed a linear relation with external strontium concentration. A direct action of strontium ions on contractile proteins (namely troponin) can be ruled out in favor of a triggering action on the sarcoplasmic reticulum, which, in turn, leads to calcium release and development of tension.Acknowledgment. I wish to thank Dr C. C. ashley in whose laboratory the research reported in this paper was performed, and Mrs L. M. Castell for invaluable technical assistance. This work was supported by grant No. 106140/048104235 from Consiglio Nazionale delle Ricerche, Italy.     

Effects of salicylate on the electrical properties of the proximal convoluted tubule of Necturus maculosus]

The effects of peritubular salicylate for chloride substitution were studied in the isolated perfused Necturus kidney. This substitution resulted in changes of cell membrane p.d., varying from tubule to tubule; the withdrawal of the test-anion invariably produced a steep and prolonged depolarization. Exposure of the tissue to salicylate brought about, in addition, electrical uncoupling of junctional membranes, which was not related to concomitant changes of membrane p.d.     

In vitro modulation of rat adipocyte ghost membrane fluidity by cholesterol oxysterols

The effects of cholesterol and cholesterol-derived oxysterols (cholestanone, cholestenone, coprostanone and epicoprostanol) on adipocyte ghost membrane fluidity were studied using a fluorescence depolarization method. The fluorescence anisotropy of the treated membranes was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Cholestanone and cholesterol decreased membranes fluidity at both the concentrations tested (10 & 50 M) while the rest of the sterols did not exert any significant effect on membrane fluidity. In the presence of epinephrine, cholestanone partitioned more towards the lipid core but cholesterol partitioning was not affected. The fusion activation energies (E) obtained for membranes preincubated with cholestanone (8.6 kcal/mol) and cholesterol (8.2 kcal/mol) were not significantly different from that of untreated membranes (8.3 kcal/mol). Membranes preincubated with cholestanone and cholesterol did not exhibit any change in lipid phase throughout the temperature range (10–45°C) tested. The sterols were found to inhibit fisetin-induced phospholipid methylation in isolated rat adipocytes in the rank order of cholesterol > epicoprostanol > cholestanone=cholestenone=coprostanone, while basal methylations was unaffected. When adipocytes were preincubated with the sterols before the addition of fisetin, cholestanone and cholestenone showed 74% and 66% inhibition of maximal methylation respectively. These results indicated that cholesterol oxysterols interact differently with rat adipocyte membranes, with cholestanone interacting more with phospholipids located at the inner lipid bilayer (e.g. phosphatidylethanolamine) while cholesterol interacts more with phosphatidylcholine located at the outer lipid bilayer. This differential interaction may cause selective changes in membrane fluidity at different depths of the bilayer and thus may modulate the activities of membrane-bound proteins such as enzymes and receptors.