Zhang H, Li P, Almassi G H, Nicolosi A, Olinger G N, Rusch N J
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Cardiovasc Pharmacol. 1996 Nov;28(5):611-7. doi: 10.1097/00005344-199611000-00002.
The saphenous vein is used extensively to test for the effects of vasodilator substances on venous reactivity, but the K+ channel types that mediate vasodilation have not been identified. Thus the goal of this study was to identify K+ channel types in vascular smooth muscle membranes of human saphenous vein (HSV), which may contribute to membrane repolarization and control of venous tone. Fourteen HSVs obtained from bypass surgery were enzymatically dissociated into single vascular myocytes for patch-clamp analysis of inside-out patches (n = 81). HSV membranes showed primarily high-conductance (226 pS) K+ channels, which accounted for > or = 95% of total patch current at physiologic voltages. Channels were highly K+ selective, showed steep voltage and Ca2+ sensitivity, and were blocked by 100 nM iberiotoxin and < or = 1 mM tetraethylammonium (TEA). These Ca(2+)-sensitive channels (KCa) also showed stacked openings in depolarized patches exposed to 300-1,000 nM calcium, suggesting multiple functional KCa channels in a single membrane patch. In tension-recording studies, isolated segments of HSV exposed to 100 nM norepinephrine contracted further during progressive block of KCa channels by 0.1-3 mM TEA, suggesting that KCa channels are pathways for repolarization and vasodilation in HSV smooth muscle cells. Our finding of KCa channels in smooth muscle membranes of HSV, if extended to the plasma membranes of other human peripheral veins, suggests that this channel may represent a therapeutic site for alleviation of conditions of increased venous tone.
大隐静脉被广泛用于测试血管舒张物质对静脉反应性的影响，但介导血管舒张的钾通道类型尚未明确。因此，本研究的目的是确定人隐静脉（HSV）血管平滑肌膜中的钾通道类型，这些通道可能有助于膜复极化和静脉张力的控制。从搭桥手术中获取的14条HSV经酶解分离成单个血管肌细胞，用于对向外膜片进行膜片钳分析（n = 81）。HSV膜主要显示高电导（226 pS）钾通道，在生理电压下该通道占总膜片电流的≥95%。这些通道对钾具有高度选择性，表现出陡峭的电压和钙敏感性，并被100 nM埃博毒素和≤1 mM四乙铵（TEA）阻断。这些钙敏感通道（KCa）在暴露于300 - 1000 nM钙的去极化膜片中也显示出叠加开放，提示单个膜片中存在多个功能性KCa通道。在张力记录研究中，暴露于100 nM去甲肾上腺素的HSV分离段在被0.1 - 3 mM TEA逐步阻断KCa通道期间进一步收缩，提示KCa通道是HSV平滑肌细胞复极化和血管舒张的途径。我们在HSV平滑肌膜中发现KCa通道，如果这一发现扩展到其他人类外周静脉的质膜，提示该通道可能是缓解静脉张力增加状况的治疗靶点。
