Ca2+-activated K+ conductance of the human red cell membrane: voltage-dependent Na+ block of outward-going currents

Human red cells were prepared with various cellular Na+ and K+ concentrations at a constant sum of 156 mM. At maximal activation of the K+ conductance. gK(Ca). the net efflux of K+ was determined as a function of the cellular Na+ and K+ concentrations and the membrane potential. Vm, at a fixed [K+]ex of approximately 3.5 mM. Vm was only varied from (Vm-EK) approximately equal to 25 mV and upwards, that is, outside the range of potentials with a steep inward rectifying voltage dependence (Stampe & Vestergaard-Bogind, 1988). gK(Ca) as a function of cellular Na+ and K+ concentrations at Vm = -40.0 and 40 mV indicated a competitive, voltage-dependent block of the outward current conductance by cellular Na+. Since the present Ca2+-activated K+ channels have been shown to be of the multi-ion type, the experimental data from each set of Na+ and K+ concentrations were fitted separately to a Boltzmann-type equation, assuming that the outward current conductance in the absence of cellular Na+ is independent of voltage. The equivalent valence determined in this way was a function of the cellular Na+ concentration increasing from 0.5 to 1.5 as this concentration increased from 11 to 101 mM. Data from a previous study of voltage dependence as a function of the degree of Ca2+ activation of the channel could be accounted for in this way as well. It is therefore suggested that the voltage dependence of gK(Ca) for outward currents at (Vm-Ek) greater than 25 mV reflects a voltage-dependent Na+ block of the Ca2+-activated K+ channels.