The human red cell voltage-regulated cation channel.: The interplay with the chloride conductance, the Ca2+-activated K+ channel and the Ca2+ pump

The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was Slow (t(1/2) about 30 s), whereas the deactivation was fast (t(1/2) about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl- concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gardos channel elicited by Ca2+ influx via the cation channel and ensuing efflux via the Ca2+ pump. Thus, the voltage-dependent cation channel, the Gardos channel and the Ca2+ pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.