Channelpedia

PubMed 17615684


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK3



Title: Cardioprotective effects of BMS-180448, a prototype mitoK(ATP) channel opener, and the role of salvage kinases, in the rat model of global ischemia and reperfusion heart injury.

Authors: Ju-Han Lee, In-Sang Jung, Sung-Hun Lee, Min-Kyu Yang, Ji-Hye Hwang, Hak-Dong Lee, Yu-Sun Cho, Min-Jin Song, Kyu-Yang Yi, Sung-Eun Yoo, Suk-Hyung Kwon, Bokyung Kim, Chang-Soo Lee, Hwa-Sup Shin

Journal, date & volume: Arch. Pharm. Res., 2007 May , 30, 634-40

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17615684


Abstract
To investigate the involvement of reperfusion-induced salvage kinases (RISK) as possible signaling molecules for the cardioprotective effects of BMS-180448, a prototype mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel opener, we measured its cardioprotective effects in a rat model of ischemia/reperfusion (I/R) heart injury, together with western blotting analysis of five different signaling proteins. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, BMS-180448 (1, 3 and 10 microM) significantly increased reperfusion left ventricular developed pressure (LVDP) and 30-min reperfusion double product (heart rate x LVDP) in a concentration-dependent manner, while decreasing left ventricular end-diastolic pressure (LVEDP) throughout reperfusion period in a concentration-dependent manner. SDS-PAGE/western blotting analysis of left ventricle reperfused for 30 min revealed that BMS-180448 significantly decreased phospho-GSK3beta at high concentration, whereas it tended to increase slightly phospho-eNOS and phospho-p70S6K with concentration. However, BMS-180448 had no effect on phospho-Akt and phospho-Bad. These results suggest that the cardioprotective effects of BMS-180448 against I/R heart injury may result from direct activation of mitoK(ATP) channel in cardiomyocytes, with the minimal role of RISK pathway in the activation of this channel and the cardioprotective effects of BMS-180448.