KMUP-1 Prevents the Cerebrovascular K+-Channel Dysfunction After Experimental Subarachnoid Hemorrhage

• Main Authors: Yi-Lin Tsai, 蔡易霖
• Other Authors: 吳炳男
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/99937970593912462372

碩士 === 高雄醫學大學 === 藥理學研究所碩士班 === 94 === Cerebral vasospasm after aneurismal subarachnoid hemorrhage (SAH) is characterized by diffuse and long-lasting narrowing of arteries. The large conductance Ca2+-activated K+ (BKCa) channel plays a negative feedback role to prevent vasospasm. KMUP-1, a xanthine-based derivative, has been demonstrated to activate K+ channels resulting in the relaxation of aortic and tracheal smooth muscles. In this study, we tried to investigate whether SAH-induced vasospasm could be a defect in the function of vascular BKCa channels, and therefore to explore the protective activity of KMUP-1 in SAH rats. Rats were divided into four groups including control, SAH, KMUP-1-treated and pinacidil-treated groups. Rats were subjected to experimental SAH by injecting autologous blood into the cisterna magna, then KMUP-1 (1 mg/kg) and pinacidil (1 mg/kg) were administered intraperitoneally at 1 h after SAH in this study. All rats were sacrificed at 24 h after SAH in this study. Cerebrovascular smooth muscle cells (CVSMCs) were enzymatically isolated from rat basilar arteries. Using whole-cell patch-clamp techniques, the iberiotoxin (IbTX)-sensitive BKCa currents attenuated in SAH groups compared with control groups. Pretreatment with KMUP-1 or pinacidil, the IbTX-sensitive currents were restored. In inside-out patches, the unitary conductance and voltage sensitivity of SAH, KMUP-1 and pinacidil groups showed effects similar to the results of control groups. However, the BKCa channel open probability (NPo) and calcium sensitivity were decreased in SAH groups compared with control groups. In conclusion, we suggest that the down-regulation of the BKCa channel activity could be due to the modification of the BKCa channel’s calcium sensitivity. From the results indicated that KMUP-1 and pinacidil could protect against SAH-induced vasospasm.