Maxi K+ channels in leaky epithelia are regulated by intracellular Ca2+, pH and membrane potential.

We have studied a Ca2+-activated K+ channel in the ventricular membrane of the epithelium of choroid plexus by means of the patch-clamp technique, using excised inside-out patches. The channel was highly K+ selective. It had a conductance of approximately 200 pS with 112 mM KCl on both sides of the membrane. The probability for the channel being open increased with intracellular Ca2+, pH and with membrane potential. The channel shows two gating modes. The primary gating mode has open and closed times which depend strongly on membrane potential, intracellular Ca2+ and pH. It accounts for the variation of the channel open probability. Lowering intracellular pH from 7.4 to 6.4 reduced the channel open probability mainly by increasing the channel closed time. It appears, that H+ can compete with Ca2+ in binding to the same site, thereby preventing channel opening. A second gating mode consisted of short-lived closures, or flickers. The open and closed time for this process were largely independent of membrane potential, intracellular Ca2+ and pH. The channel density was approximately 0.4 micron-2 corresponding to a K+-permeability of 2.2 10(-5) cm s-1 if the channels were fully open. In cell-attached patches we measured the open probability of the channel in the intact cell membrane. The channel is almost totally closed under normal cellular conditions. This type of channel is therefore not the membrane component that forms the electrodiffusive pathway for K+-ions.