Small conductance Ca2+-activated K+ channels are regulated by Ca2+-calmodulin-dependent protein kinase II in murine...

1. Ca2+ regulates the activity of small conductance Ca2+-activated K+ (SK) channels via calmodulin-dependent binding. We investigated whether other forms of Ca2+-dependent regulation might control the open probability of SK channels. 2. Under whole-cell patch-clamp conditions, spontaneous openings of SK channels can be resolved as charybdotoxin-insensitive spontaneous transient outward currents (STOCs). The Ca2+-calmodulin-dependent (CaM) protein kinase II inhibitor KN-93 reduced the occurrence of charybdotoxin-insensitive STOCs. 3. The charybdotoxin-insensitive STOCs are related to spontaneous, local release of Ca2+. KN-93 did not affect spontaneous Ca2+-release events. 4. KN-93 and W-7, a calmodulin inhibitor, decreased the open probability of SK channels in on-cell patches but not in excised patches. 5. Application of autothiophosphorlated CaM kinase II to the cytoplasmic surface of excised patches increased the open probalibity of SK channels. Boiled CaM kinase II had no effect. 6. We conclude that CaM kinase II regulates SK channels in murine coloni myocytes. This mechanism provides a secondary means of regulation, increasing the impact of a given Ca2+ transient on SK channel open probability.