Modulation of ATP-Induced Activation of the Muscarinic K⁢ Channel Activity by Protein Kinase C

• 영문명: Modulation of ATP-Induced Activation of the Muscarinic K^⁢ Channel Activity by Protein Kinase C
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yang-Mi Kim Hong-Ki Park Jae-Hee Han Choon-Ok Park Seong-Geun Hong
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제2권 제6호, 743~753쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1998.01.01

영문 초록

The atrial acetylcholine-activated K^⁢ (K_ACh) channel is gated by the pertussis toxin-sensitive inhibitory G (G_K) protein. Earlier studies revealed that ATP alone can activate the K_ACh channel via transphosphorylation mediated by nucleoside-diphosphate kinase (NDPK) in atrial cells of rabbit and guinea pig. This channel can be activated by various agonists and also modulated its function by phosphorylation. ATP-induced K_ACh channel activation (AIKA) was maintained in the presence of the NDPK inhibitor, suggesting the existence of a mechanism other than NDPK-mediated process. Here we hypothesized the phosphorylation process as another mechanism underlying AIKA and was undertaken to examine what kinase is involved in atrial cells isolated from the rat heart. Single application of 1 mM ATP gradually increased the activity of K_ACh channels and reached its maximum 40∼50 sec later following adding ATP. AIKA was not completely reduced but maintained by half even in the presence of NDPK inhibitor. Neither ADP nor a non-hydrolyzable ATP analogue, AMP-PNP can cause AIKA, while a non-specific phosphatase, alkaline phosphatase blocked completely AIKA. PKC antagonists such as sphingosine or tamoxifen, completely blocked AIKA, whereas PKC catalytic domain increased AIKA. Taken together, it is suggested that the PKC-mediated phosphorylation is partly involved in AIKA.

키워드

muscarinic K^⁢ channel PKC ATP Phosphorylation Atrial myocytes