A XANTHINE DERIVATIVE ON LARGE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CURRENTS IN RAT BASILAR ARTERY

• Main Authors: HSIAO-FANG TU, 涂筱芳
• Other Authors: ING-JUN CHEN
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/44713911042660490016

碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 92 === KMUP-1, a chemically synthetic xanthine-based derivative, has been demonstrated not only increase of cyclic nucleotides and K+ channels, but also inhibition of phosphodiesterases in rat aortic smooth muscle (SM), rabbit corpus cavernosum and guinea-pig tracheal SM. The aim of this study was further to investigate the ionic mechanisms of KMUP-1 whether and by what signaling to stimulate K+ efflux in rat basilar arteries. Cerebral myocytes were enzymatically isolated from rat basilar arteries. KMUP-1 (1 microM) did not affect the delay-rectifying potassium (KDR) currents, but significantly increased the large-conductance Ca2+-activated potassium (BKCa) currents using conventional voltage-clamp techniques. In cell-attached or inside-out configuration, the opening probability of BKCa channels by KMUP-1 was measured and it did markedly increase the channel opening probability. To study the mechanisms of KMUP-1 on BKCa channels, a soluble guanylate cyclase (sGC) inhibitor ODQ (10 microM), an adenylate cyclase (AC) inhibitor SQ 22536 (100 microM), the cGMP- and cAMP-dependent protein kinase inhibitors KT5823 (300 nM) and KT5720 (300 nM), and the competitive cGMP and cAMP antagonists Rp-cGMP (100 microM) and Rp-cAMP (100 microM) were applied. The increasing activities of BKCa currents by KMUP-1 were significantly attenuated by all of these agents. In conclusion, KMUP-1 increases the BKCa currents and the channels open probability, thus, suggesting that it activates both sGC/cGMP/PKG and AC/cAMP/PKA cascades resulting in hyperpolarization of the cell membrane in basilar artery myocytes.