Transient outward potassium current in ICC

Interstitial cells of Cajal (ICC) are the pacemakers of the gut, initiating slow-wave activity. Several ion channels have been identified that contribute to the depolarization phase of the slow wave. Our aim was to contribute to knowledge about the identity and role of ICC potassium channels in pacemaking. Here we describe a transient outward potassium current in cell-attached patches of ICC. This current was activated almost instantaneously at potentials positive of the resting membrane potential and inactivated as a single exponential or biexponential with time constants that varied widely from patch to patch. Averaged traces gave a biexponential inactivation with time constants of approximately 40 and approximately 500 ms, with no clear voltage dependence. Analysis of single-channel openings and closings indicated a channel conductance of 5 pS and permeability sequence of K(+) (111) > Na(+) (1) > N-methyl-d-glucamine(+) (0.11). The current was completely blocked by 20 microM clotrimazole but was unaffected by 20 microM ketoconazole, 10 microM E4031, or 20 microM clofilium; 5 mM 4-aminopyridine slowed the activation of the current. The transient outward current may be important in moderating the upstroke of the pacemaker potential.