Closed-state inactivation induced in K(V)1 channels by extracellular acidification

Extracellular acidification regulates the biophysical properties of many voltage-gated potassium channels. Most often acidic pH reduces peak current and enhances current decay during depolarization. Here we review recent data from single channel and voltage clamp fluorimetry studies, which suggest that these two effects of protons are mediated by distinct kinetic processes. This new mechanistic insight directly demonstrates that whilst the enhanced decay of current observed with acidic pH is due to an accelerated entry of open channels into P/C-type inactivation, the main mechanism for the reduction in peak channel conductance is a stabilization of resting channels in closed-inactivated states. Thus acidic pH acts to reduce the mean burst time of conducting channels, as well as to prevent other channels from opening at all, and in so doing, reveals that both open- and closed-state inactivation processes can co-exist in K(V) channels.