An upper limit for the electrogenic Na–K pump contribution to maximum diastolic potential in feline cardiac Purkinje fibers in steady state

We have estimated an upper limit for the electrogenic contribution of the Na–K pump to diastolic transmembrane potential. We simultaneously monitored the maximum diastolic potential and the extracellular space potassium activity during exposure to a very high concentration of ouabain. Exposure to ouabain caused a depolarization of approximately 3 mV (n = 33 experiments) over 34 ± 3 s (mean ± standard error) prior to any change in extracellular K activity. In four experiments, we monitored intracellular sodium activity and observed it to rise with approximately the same temporal lag (delay = 26 ± 7 s). We also measured relative membrane conductance in one series of experiments and observed it to decrease to 91 ± 2% of its control value by the time extracellular space K began to rise. Following the initial increase in extracellular space K activity the subsequent membrane depolarization is shown to be accurately predicted solely from the measured increase in extracellular space K activity as calculated from the Goldman equation. Limitations of the method and possible interpretations of the data are discussed. We interpret this ouabain-induced depolarization that occurs prior to the rise in external K to be an upper limit to the Na–K pump's electrogenic contribution to steady-state membrane potential.

Influence of the intracellular and extracellular cation concentration on monovalent cation efflux of resealed human erythrocyte ghosts

Tracer efflux measurements (86Rb+ and2NaNa+) were performed on resealed human erythrocyte ghosts at different intra- and extracellular NaCI concentrations. Using a modified Goldman equation the observed alterations of the rate constants could be explained by taking into account the transmembrane and surface potentials, at constant permeability coefficient. These results emphasize the importance of membrane surface potentials in triggering ion transport across biological membranes.

Responses of Regularly-Firing Aplysia R3-R13 Neurones to Normoxia and Hypoxia

1. Exposure of 10 R3-R13 neurones to a 115-min period of hypoxia resulted in depolarization of their membrane potentials (EM) from a mean of −46.9±3.1 to −20.8±4.4mV (S.E.). 2. Intracellular potassium ion activities (aiK) decreased significantly from 118.9±5.1 to 67.7±8.5mM-K+. This is equivalent to a change in EK from −70.9 mV to −54.5 mV, which is insufficient to account for depolarization of approximately 26 mV. 3. During reoxygenation of the saline surrounding the ganglion, there was a continued depolarization of EM to −11.5 ± 3.2 mV and progressive fall in aiK to 49.2 ± 4.9 mM. 4. Decreases in the membrane slope resistance were also observed in these depolarizing neurones. The depression in resistance remained irreversible for as long as experiments were conducted. 5. Computations of PNa/PK ratios were made using a steady-state calculation. Increases in the PNa/PK ratio from 0.030 to 0.045 were observed during hypoxic depolarization using a modification of the Goldman equation which neglects the contribution of chloride ions. Subsequent depolarization and loss of aiK during reoxygenation elevated this value to 0.183. Whether or not the observed depression of the membrane resistance is linked to a change in either the sodium or potassium ion permeability is unknown. Release of neuro transmitter and related permeability changes cannot be ruled out as an effect of hypoxia.

Reversible changes in the intracellular potassium ion activities and membrane potentials of Aplysia L2-L6 neurones in response to normoxia and hypoxia

1. Exposure of 7 L2-L6 neurones to hypoxia for 65 min resulted in hyperpolarization of the membrane potential (EM) from a mean of −49.1 +/− 2.1 to −54.1 +/− 3.6 mV (S.E.). 2. Intracellular potassium ion activities (aiK) increased significantly from 137.7 +/− 4.0 to 155.6 +/− 3.4 mM-K+. This is equivalent to a change in EK from −74.2 mV commensurate with the observed hyperpolarization of 5 mV. 3. The reversibility of these responses was noted by reoxygenating the solution surrounding the ganglion for a period of 55 min. 4. In another group (n = 7) of L2-L6 neurones, the responses in aiK, EM, and EK were slower, although following hypoxia for 90–110 min, similar changes in the levels of these membrane phenomena were recorded. 5. PNa/PK ratios were computed for both L2-L6 groups of neurones using a modified version of the Goldman equation. There were only slight decreases in this ratio with hypoxia, which were not significantly different from the control (normoxia). Therefore, we conclude that this period of hypoxia is capable of stimulating the sodium pump of these cells since the membrane potentials seem to hyperpolarize according to the increase in aiK. However, tonic release of neurotransmitter, which could hyperpolarize these neurones and attract intracellular potassium, cannot be ruled out as an effect of hypoxia.

Effects of amphotericin B on the electrical properties and electrolyte content of frog sartorius muscle

We studied the effect of amphotericin B (52 μM) on the membrane potential, membrane resistance, and intracellular Na+ and K+ concentrations in isolated frog sartorius muscles to characterize further the nature of the ionic conductance induced by the antibiotic. After 5 h of exposure to amphotericin B, the membrane depolarized from −89.9 to −51.0 mV, the membrane resistance decreased from 4537 to 907 Ωcm2, [K]i decreased from 122 to 31.2 mmol/L fiber H2O, and [Na]i increased from 30.9 to 88.7 mmol/L fiber H2O. The relative sodium permeability, PNa/PK, calculated with the Goldman equation remained apparently constant at a value of 0.01 in treated and untreated muscles. We hypothesize that amphotericin B creates either a nonselective cation channel or a completely nonselective ionic leak channel whose equilibrium potential is equal or close to the membrane potential.

Dynamic oscillations in the membrane potential of pancreatic islet cells

Glucose and other metabolizable sugars which elicit insulin release from the beta-cell of the pancreatic islet induce repetitive oscillations in the beta-cell transmembrane potential. Upon each phasic depolarization are superimposed rapid fluctuations in potentials, i.e. ‘action potentials’ or ‘spikes’ which occur as bursts of electrical activity; the duration and frequency of each burst is a function of glucose concentration. These established electrophysiological features of glucose-islet cell interaction are described in detail together with a consideration of their possible molecular and ionic basis. Based on these observations, a dynamic mathematical computer model of the beta-cell membrane electrical behaviour is presented which utilizes the Goldman equation extended to include divalent ions. The model illustrates how the ionic mechanisms deduced from experimental observations can account for the electrical patterns produced by the beta-cells in the presence of D-glucose; it also allows systematic changes to be made in a number of state variables in order to assess their relative importance and possible contribution to the integrated processes actually observed. Finally, distinction is made between aspects of the model which are well supported by experimental results and those areas which require further analysis.

Permeability of the sodium channel in Myxicola to organic cations.

The relative permeability of sodium channels to organic cations was determined in the Myxicola giant axon. Ionic currents under potential control were measured in seawater and in sodium-free solutions containing the organic cation. The measured reversal potential and the Goldman equation were used to obtain the relative permeabilities. The permeability sequence was found to be: sodium greater than hydroxylamine greater than hydrazine greater than ammonium greater than guanidine greater than formamidine greater than aminoguanidine greater than methylamine. Measurements were also made on sodium and several of the organic cations at different concentrations. The relative permeabilities of the ions were found to be independent of concentration. Qualitatively, the permeability sequence for the Myxicola giant axon was similar to that of the frog node of Ranvier.