Apical K+ channels in frog skin (Rana temporaria): cation adsorption and voltage influence gating kinetics.

Open-close kinetics of fluctuating K+ channels in the apical frog skin membrane were studied with noise analysis of the K+ current (IK). The mucosa to serosa directed IK was obtained with serosal NaCl- and mucosal KCl-Ringer under voltage clamp conditions. Mucosal protons (pH greater than 4), several polyvalent metal ions, and choline shifted the plateaus (SO) of the Lorentzian component in the IK noise spectrum to higher, but the corner frequency (fc) to lower values. SO was lowered at pH less than 4, due to a K+-channel block by H+. Ca2+, Sr2+, H+ (pH greater than 4) and choline did not affect IK. A slight reduction of IK was seen with Mg2+, Mn2+, Co2+, Ni2+, Zn2+, Cu2+ and La3+. At pH greater than 4, the H+-induced shifts in SO an fc were almost abolished in solutions of high mucosal Ca2+ concentrations. Clamping the transepithelial potential difference to more positive values (with respect to the serosa) shifted the Lorentzian parameters SO and fc in the same way as the cations did. As with protons, mucosal Ca2+ interferred with the effect of voltage. The interference of cationic (probably fixed charge screening) and voltage effects suggests a common, more general mechanism of action, namely alterations in K+-channel fluctuation kinetics by changes in local electrical fields. On this basis, the rates for the open-close reaction of K+ channels and their mean lifetime were calculated. We found that e.g. increasing [Ca2+]O from 1-10 mM caused no change of the mean open time, but increased the mean time "closed" of the K+ channel by a factor of about 1.5. Other mucosal cations, as well as depolarizing clamp potentials are thought to have the same effect.