Participation of Ca2(+)-activated K+ channels in electrical activity of canine gastric smooth muscle

1. The hypothesis that Ca2(+)-activated K+ channels participate in the repolarization of electrical slow waves was tested in isolated cells and intact muscles of the canine gastric antrum. 2. Freshly dispersed cells from the gastric antrum liberally express large conductance channels that were characterized as Ca2(+)-activated K+ channels by several criteria. 3. Mean slope conductance of these channels in symmetrical 140 mM-KCl solutions was 265 +/- 25 pS and reversal potential was 1.3 +/- 3.3 mV. The reversal potential was shifted when K+ was partially replaced with Na+ in a manner consistent with the Nernst equation for the K+ gradient. 4. Open probability was studied in excised patches in solutions containing 10(-7)-10(-6) M-Ca2+ with holding potentials ranging from -100 to +100 mV. Resulting activation curves were fitted by Boltzmann functions. 5. Increasing [Ca2+] from 10(-7) to 10(-6) M shifted the half-maximal activation from +99 to 0 mV. These data suggest that Ca2(+)-activated K+ channels may be activated in the voltage range and [Ca2+]i occurring during the plateau phase of the slow wave. 6. In intact muscles loaded with the photolabile Ca2+ chelator, nitr-5, photo-activated release of Ca2+ during the slow wave cycle produced changes consistent with activation of Ca2(+)-dependent outward currents. 7. The data are consistent with the idea that Ca2+ build-up during electrical slow waves shifts the activation voltage of Ca2(+)-activated K+ channels into the range of the plateau potential. Activation of these channels yields outward current and repolarization. 8. Since the force of contractions depends on slow wave amplitude and duration, regulation of these channels may be important in controlling gastric motility.