A non‐selective cation conductance in frog muscle membrane blocked by micromolar external calcium ions.

Abstract

Membrane currents were recorded from voltage-clamped, ethylene glycol-bis(.beta.-aminoethyl ether) N,N,N''N''-tetraacetic acid [EGTA]-loaded muscle fibers under conditions where currents through ordinary Na+, K+ and Cl- channels were prevented by drugs or by absence of permeant ions (K+ and Cl-). At 10 mM-external [Ca2+], substitution of Na+ for the large and presumably impermeant organic cations tetramethyl- (TMA+) or tetraethylammonium (TEA+) failed to increase peak inward current. Hence, the Ca2+ channel was not significantly permeable to Na+ under these conditions. When external [Ca2+] was reduced to levels below 1 .mu.M in the presence of external Na+, step depolarizations to negative potentials produced tetrodotoxin-resistant inward currents. At -20 mV, they rose to a peak of 30-200 .mu.A/cm2 within 150 ms and declined thereafter. Ca2+ and several other divalent cations reversibly blocked this inward current. The sequence of blocking potencies was Ca2+ > Sr2+ .gtoreq. Co2+ > Mn2+ > Mn2+ .simeq. Cd2+ > Ni2+ .simeq. Mg2+. Large inward currents may be carried by Li+, Na+, K+, Rb+ and Cs+, but not by TMA+ and TEA+. The effect of external Ca2+ ([Ca2+]o) was explored over a 108-fold range in concentrations. Na+ was present at a fixed concentration. When [Ca2+]o was gradually increased from 10-10 to 10-2 M, inward current first diminished 10-fold, reached a mininum at [Ca2+]o = 60 .mu.M and then increased again as [Ca2+]o was increased further and Ca2+ itself became a current carrier. Block of inward current at [Ca2+]o < 10-5 M could be described by binding of a single Ca2+ to a site, with a Kd of the order of 0.7 .mu.M at -20 mV.