Internal Ca2+ ions inactivate and modify ATP-sensitive potassium channels in adult mouse skeletal muscle

The effects of internal Ca2+ ions on single ATP-sensitive potassium channels (KATP channels) were studied in inside-out membrane patches excised from mouse skeletal muscle. Channel activity was high when patches were excised in a Ca(2+)-free, Na(+)-rich solution and declined irreversibly within seconds in the presence of internal Ca2+ (0.1 and 2 mM). After Ca(2+)-dependent inactivation of the channels, the ATP concentration-response curve was steeper and 50% channel blockage occurred at a lower ATP concentration than before inactivation. ATP (50 microM) in a K(+)-rich solution bathing the intracellular membrane surface reduced the open-probability of KATP channels to 18% before and to 10% after exposure of the patch to internal Ca2+ (0.1 mM). The block of KATP channels by ATP (50 microM) was also enhanced by internal Ca2+ at a concentration of 13 microM. It is concluded that internal Ca2+ ions can both inactivate KATP channels and modify the active channels. KATP channels modified by Ca2+ are blocked more strongly by ATP than unmodified channels.