Referenced in: none

Automatically associated channels: Kir6.2

Title: Proteasomal degradation of Kir6.2 channel protein and its inhibition by a Na+ channel blocker aprindine.

Authors: Hiroaki Tanaka, Junichiro Miake, Tomomi Notsu, Kazuhiko Sonyama, Norihito Sasaki, Kazuhiko Iitsuka, Masaru Kato, Shin-ichi Taniguchi, Osamu Igawa, Akio Yoshida, Chiaki Shigemasa, Yoshiko Hoshikawa, Yasutaka Kurata, Akihiko Kuniyasu, Hitoshi Nakayama, Nobuo Inagaki, Eiji Nanba, Goshi Shiota, Takayuki Morisaki, Haruaki Ninomiya, Masafumi Kitakaze, Ichiro Hisatome

Journal, date & volume: Biochem. Biophys. Res. Commun., 2005 Jun 17 , 331, 1001-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15882977

Abstract
ATP-sensitive K+ channels (K(ATP):SUR2A+Kir6.2) play a pivotal role in cardiac protection against ischemia and reperfusion injury. When expressed in COS cells, Kir6.2 was short-lived with a half-life time of 1.9 h. The half-life time of Kir6.2 was prolonged by proteasome inhibitors MG132, ALLN, proteasome inhibitor 1, and lactacystine, but not at all by a lysosomal inhibitor chloroquine. MG132 also increased the level of ubiquitinated Kir6.2 without affecting its localization in the endoplasmic reticulum and Golgi apparatus. In electrophysiological recordings, MG132 augmented nicorandil-activated K(ATP) currents in COS cells expressing SUR2A and Kir6.2 as well as the same currents in neonatal rat cardiomyocytes. Like MG132, a Na+ channel blocker aprindine prolonged the half-life time of Kir6.2 and augmented K(ATP). Finally, both aprindine and MG132 inhibited the 20S proteasome activity in vitro. These results suggest a novel activity of aprindine to enhance K(ATP) currents by inhibiting proteasomal degradation of Kir 6.2 channels, which may be beneficial in the setting of cardiac ischemia.