Cox Robert H
Lankenau Institute for Medical Research, Jefferson Health System, 100 West Lancaster Avenue, Wynnewood, Philadelphia, PA 19096, USA.
Vascul Pharmacol. 2002 Jan;38(1):13-23. doi: 10.1016/s1537-1891(02)00122-2.
Altered function of K+ channels associated with hypertension has been inferred from the effects of K+ channel blockers on contraction of arterial smooth muscle cells (SMCs) and from K+ efflux measurements. Of the classes of K+ channels known to exist in the smooth muscle, the contribution of voltage-gated (KV) and high-conductance, Ca2+ gated K+ (BKCa) channels to the regulation of arterial SMC contractile function has been the most studied in hypertension. The effects of selective and nonselective K+ channel blockers on tonic contraction suggest that these two K+ channel gene families contribute differently to total K+ conductance in arterial SMCs from normal and hypertensive subjects. Direct measurements of K+ channel properties by electrophysiological methods generally support this conclusion. Studies have demonstrated larger BKCa currents in SMCs from several arteries of hypertensive rats, which have been reported to result from a greater Ca2+ sensitivity of BKCa channels and/or from greater protein expression. Some, but not all, studies have shown decreased KV currents in arterial SMCs from hypertensive animals measured under Ca(2+)-replete conditions. However, when external Ca2+ is removed or when Ca2+ influx is inhibited, KV currents are larger in SMCs exposed to chronic hypertension. Gene expression studies of Shaker KV1 transcripts have shown that of the dominant species present in arterial SMCs, KV1.2 expression is higher, whereas KV1.5 is the same in SMCs from hypertensive compared to normal animals. This finding is consistent with the larger KV currents in vascular SMCs from hypertensive animals under low Ca2+ conditions and suggests that Ca2+ influx and/or intracellular Ca2+ per se exerts a greater inhibitory effect on KV currents in the myocytes from these animals. The pathways by which these K+ channel differences are produced during hypertension remain to be elucidated, as does the potential for these channel proteins to be targeted by novel antihypertensive therapies.
钾通道功能改变与高血压相关，这是从钾通道阻滞剂对动脉平滑肌细胞（SMC）收缩的影响以及钾外流测量结果推断出来的。在已知存在于平滑肌中的各类钾通道中，电压门控（KV）通道和高电导、钙门控钾（BKCa）通道对动脉SMC收缩功能调节的作用在高血压研究中最为深入。选择性和非选择性钾通道阻滞剂对张力性收缩的影响表明，这两个钾通道基因家族对正常和高血压受试者动脉SMC的总钾电导贡献不同。通过电生理方法直接测量钾通道特性通常支持这一结论。研究表明，高血压大鼠多条动脉的SMC中BKCa电流更大，据报道这是由于BKCa通道对钙的敏感性更高和/或蛋白质表达增加所致。一些（但不是全部）研究表明，在钙充足条件下测量的高血压动物动脉SMC中KV电流降低。然而，当去除细胞外钙或抑制钙内流时，暴露于慢性高血压的SMC中KV电流更大。对Shaker KV1转录本的基因表达研究表明，在动脉SMC中存在的主要类型中，KV1.2的表达更高，而与正常动物相比，高血压动物SMC中KV1.5的表达相同。这一发现与低钙条件下高血压动物血管SMC中更大的KV电流一致，表明钙内流和/或细胞内钙本身对这些动物心肌细胞中的KV电流具有更大的抑制作用。高血压期间产生这些钾通道差异的途径仍有待阐明，这些通道蛋白作为新型抗高血压疗法靶点的潜力也有待阐明。
