Modulation of a cloned mouse brain potassium channel

The mouse brain K⁺ channel (MBK), previously cloned by others, has been independently cloned and shown to express in Xenopus oocytes. This K⁺ current (I_K) inactivated over a time course of seconds and was sensitive to the K⁺ channel-blocking reagent tetraethylammonium. When the K⁺ channel was coexpressed with a cloned mouse brain serotonin receptor (5HT_1c) in oocytes, activation of the 5HT_1c receptor by a brief application of serotonin resulted in a suppression of the I_K amplitude over the next 20 min. I_K could also be suppressed by activation of G proteins. Suppression was also caused by intracellular Ca²⁺ injections and was blocked by intracellular injection of EGTA. Calmodulin antagonists block the I_K suppression, but a known protein kinase inhibitor did not block suppression. The 5HT_1c suppression was reversible; recovery from suppression was blocked by the protein kinase inhibitor H-7. These data suggest that the I_K suppression occurs through a novel mechanism independent of A- or C-type protein kinases; suppression is best explained as being due to the action of a Ca²⁺/calmodulin-activated phosphatase; recovery from suppression is due to the action of a protein kinase.