Current-voltage relations of Cs+-inhibited K+ currents through the apical membrane of frog skin

The voltage-dependence of the inhibitory effect of mucosal Cs+ on the inward K+ current through the apical membrane of frog skin (Rana temporaria) was studied by recording transepithelial current-voltage relations. Experiments were performed with skins exposed to NaCl and KCl Ringer solutions on the serosal and mucosal side respectively (control skins), as well as with tissues incubated with K2SO4 Ringer solutions on both sides (depolarized skins). Studies of the dose-dependence of the Cs+ block showed that under both experimental conditions the apparent affinity of Cs+ increased as the transepithelial potential was clamped at higher mucosal positive voltages. Under control conditions, the concentration of Cs+ required to block 50% of the K+ current (KCs) recorded while the transepithelial voltage was clamped at zero mV was 16 mmol/l. KCs decreased exponentially with mucosal positive voltages. The dependence of KCs on the membrane potential was analyzed with Eyring rate theory in which Cs+ was assumed to block the K+ transport by binding to a site within the channel. The analysis showed that this site is located at a relative electrical distance delta = 0.32 of the voltage drop across the apical membrane, measured from the cytosolic side. The Hill coefficient obtained from this analysis was n = 3.1. Experiments with K+-depolarized tissues showed that only inward K+ currents recorded with positive transepithelial voltages were depressed by external Cs+. Also under these conditions KCs showed an exponential dependence on the transepithelial potential. The analysis of these data with the rate theory revealed delta = 0.09 and n = 1.7.(ABSTRACT TRUNCATED AT 250 WORDS)