Divalent Cations

AB STRACT The effects of external Zn+2 and other divalent cations on K channels in squid giant axons were studied. At low concentration (2 mM) Zn+2 slows opening kinetics without affecting closing kinetics . Higher concentrations (5-40 mM) progressively slow opening and speed channel closing to a lesser degree. In terms of "shifts," opening kinetics are strongly shifted to the right on the voltage axis, and OFF kinetics much less so . The shift of the conductancevoltage relation along the axis is intermediate . Zinc's kinetic effects show little sign ofsaturation at the highest concentration attainable . Zn does not alter the shape of the instantaneous current-voltage relation of open channels . Some other divalent cations have effects similar to Zn+2, Hg2+ being the most potent and Ca12 the least . After treatment with Hg+2, which is irreversible, Zn+2 still slows opening kinetics, which suggests that each channel has at least two sites for divalent cation action . The results are not compatible with a simple theory of fixed, uniform surface charges. They suggest that external cations interact directly with a negatively charged element of the gating apparatus that moves inward from the membrane's outer surface during activation . Examination of normal kinetics shows that there is a slow step somewhere in the chain leading to channel opening, but the slowest step must not be the last one.