Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
J Cardiovasc Pharmacol. 2012 Jan;59(1):29-36. doi: 10.1097/FJC.0b013e318233614c.
We determined the possible role of large-conductance Ca2+-activated K (BK) channels in regulation of venous tone in small capacitance veins and blood pressure. In rat mesenteric venous smooth muscle cells (MV SMC), BK channel α- and β1-subunits were coexpressed, unitary BK currents were detected, and single-channel currents were sensitive to voltage and [Ca2+]i. Rat MV SMCs displayed Ca sparks and iberiotoxin-sensitive spontaneous transient outward currents. Under resting conditions in vitro, rat MV exhibited nifedipine-sensitive spontaneous oscillatory constrictions. Blockade of BK channels by paxilline and Ca2+ sparks by ryanodine constricted rat MV. Nifedipine caused venodilation and blocked paxilline-induced, KCl-induced (20 mM), and BayK8644-induced contraction. Acute inhibition of BK channels with iberiotoxin in vivo increased blood pressure and reduced venous capacitance, measured as an increase in mean circulatory filling pressure in conscious rats. BK channel α-subunits and L-type Ca2+ channel α1-C subunits are expressed in murine MV. However, these channels are not functional because murine MV lack nifedipine-sensitive basal tone and rhythmic constrictions. Murine MV were also insensitive to paxilline, ryanodine, KCl, and BayK8644, consistent with our previous studies showing that murine MV do not have BK β1-subunits. These data show that not only there are species-dependent properties in ion channel control of venomotor tone but also BK channels are required for rhythmic oscillations in venous tone.
我们确定大电导钙激活钾（BK）通道在调节小容量静脉和血压中的静脉张力方面可能发挥作用。在大鼠肠系膜静脉平滑肌细胞（MVSMC）中，共表达 BK 通道的α-和β1-亚基，检测到单位 BK 电流，并且单通道电流对电压和[Ca2+]i敏感。大鼠 MVSMC 显示 Ca 火花和 iberiotoxin 敏感的自发性瞬态外向电流。在体外静息条件下，大鼠 MV 表现出硝苯地平敏感的自发性振荡收缩。BK 通道的阻断剂 paxilline 和 Ca2+火花的阻断剂 ryanodine 收缩大鼠 MV。硝苯地平引起静脉舒张，并阻断 paxilline 诱导的、KCl 诱导的（20 mM）和 BayK8644 诱导的收缩。体内用 iberiotoxin 急性抑制 BK 通道会增加血压并降低静脉容量，表现为清醒大鼠的平均循环充盈压增加。BK 通道的 α-亚基和 L 型 Ca2+通道的 α1-C 亚基在鼠 MV 中表达。然而，这些通道没有功能，因为鼠 MV 缺乏硝苯地平敏感的基础张力和节律性收缩。鼠 MV 对 paxilline、ryanodine、KCl 和 BayK8644 也不敏感，这与我们之前的研究一致，表明鼠 MV 没有 BKβ1-亚基。这些数据表明，不仅离子通道对静脉张力的控制存在种属依赖性，而且 BK 通道也是静脉张力节律性振荡所必需的。
