Influence of membrane potential on calcium efflux from giant axons of Loligo.

Abstract

SUMMARY1. Experiments are described in which Ca efflux is monitored in axons under voltage clamp.2. As Ca efflux consists of more than one component, conditions were sought where one component predominates. Thus external Na-dependent Ca efflux can be studied in relative isolation either at pH 9 0 or in fully poisoned axons immersed in Ca-free media; external Ca-dependent Ca efflux can be studied in fully poisoned axons immersed in Na-free media and the Na-independent, energy requiring, pump is best examined in Na and Ca-free sea waters.3. Both in unpoisoned axons at pH 9 0 and fully poisoned axons at pH 7-8, the external Na-dependent Ca efflux is activated by hyperpolarization and inhibited by depolarization. Depolarizations achieved either electrically or by exposure to high K are roughly comparable and the inhibition brought about by high K can largely be removed by electrical hyperpolarization to the initial resting potential. In both Na sea waters and choline sea waters containing 100 mM-Na, Ca efflux is increased e-fold over approximately 50 mV.4. In choline sea water, external Ca-dependent Ca efflux from fully poisoned axons is unaffected by voltage over the range -80 to -30 mV. But addition of K or Li activates the flux and this activation is increased by hyperpolarization and decreased by depolarization, suggesting that the activating cation may also be transported into the axon. 5. The Na-independent, energy-requiring, flux is inhibited by electrical hyperpolarization and stimulated by electrical depolarization. External K also stimulates the flux and part of this stimulation can be removed by electrical hyperpolarization. These data show that the energy-dependent pump is sensitive to membrane potential in the physiological range and suggest that it may be an electrogenic process.6. The finding that voltage affects the energy-dependent (uncoupled) pump and external Na-dependent fluxes in opposite directions may help explain why the total Ca efflux from intact axons responds to potential in a very variable manner.

Comparison of the effects of potassium and membrane potential on the calcium‐dependent sodium efflux in squid axons.

“…In the following paper (Allen & Baker, 1986) we present some data consistent with transport of a monovalent cation involved in activation of external Ca-dependent Ca efflux, and Ehrlich & Russell (1984) have described a Li influx into squid axons that is absolutely dependent on internal Na. Unfortunately they did not examine its sensitivity to external Ca.…”

Inactivation of outward Na(+)‐Ca2+ exchange current in guinea‐pig ventricular myocytes.

“…7C for intact myocytes, a decrease of the extracellular Ca2+ concentration from 1 to 0-1 mm did not reduce voltage dependence significantly in the presence of Li+. Neither a change of the extracellular Ca2' affinity per se (Allen & Baker, 1986a) Allen & Baker (1986b) reported that Ca2+-Ca2+ exchange was voltage independent in the absence of monovalent cations. Obviously, much further work is necessary to cla.rify how monovalent cations act and how these actions are related to the inherent electrogenicity of the Na+-Ca2+ exchange cycle.…”

Electrogenic properties of the Na:Ca exchange

“…The exact number, however, has been the subject of much debate, principally because of the problems involved in the isolation of Na + and Ca 2+ fluxes through the exchange mechanism from those through other membrane pores and carriers. In the squid axon, for instance, flux measurements are consistent with 2-5 Na + ions exchanging with each Ca 2+ ion (Baker et al, 1969;Allen & Baker, 1986b therefore, that the movement of ions through the exchange mechanism is tightly coupled according to a stoichiometry which is fixed over a wide range of conditions.…”

“…This outward current is likely to reflect the reversed mode of the exchange, mediating Ca influx, since it is reduced by a decrease in [Ca]o or [Na]; and blocked by La. The activation of the outward current also requires a low concentration of internal Ca, a property of Nadependent Ca influx observed in the squid axon (Dipolo & Beauge, 1983;Allen & Baker, 1986b). Since the exchange process is reversible, one might ex- Egan et al, 1989) pect that the reversal of the ionic gradients across the membrane will generate an inward current.…”