Ca(2+)/calmodulin regulates Kv?1.1-mediated inactivation of voltage-gated K(+) channels.

ABSTRACT: A-type K(+) channels open on membrane depolarization and undergo subsequent rapid inactivation such that they are ideally suited for fine-tuning the electrical signaling in neurons and muscle cells. Channel inactivation mostly follows the so-called ball-and-chain mechanism, in which the N-terminal structures of either the K(+) channel's ? or ? subunits occlude the channel pore entry facing the cytosol. Inactivation of Kv1.1 and Kv1.4 channels induced by Kv?1.1 subunits is profoundly decelerated in response to a rise in the intracellular Ca(2+) concentration, thus making the affected channel complexes negative feedback regulators to limit neuronal overexcitation. With electrophysiological and biochemical experiments we show that the Ca(2+) dependence is gained by binding of calmodulin to the "chain" segment of Kv?1.1 thereby compromising the mobility of the inactivation particle. Furthermore, inactivation regulation via Ca(2+)/calmodulin does not interfere with the ? subunit's enzymatic activity as an NADPH-dependent oxidoreductase, thus rendering the Kv?1.1 subunit a multifunctional receptor that integrates cytosolic signals to be transduced to altered electrical cellular activity.

SUBMITTER: Swain SM 

PROVIDER: S-EPMC4614385 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature