Christ G J
Department of Urology, and Institute for Smooth Muscle Biology, Laboratory of Molecular and Integrative Urology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Drug News Perspect. 2000 Feb;13(1):28-36.
Changes in the contractile status (i.e., contraction and relaxation) of corporal and arterial smooth muscle cells (myocytes) govern the flow of blood to and from the penis and, thus, ultimately have a major impact on erectile capacity. As with many other smooth muscle cell types, corporal myocyte contractility is inextricably linked to ion channel activity. Corporal smooth muscle cells possess a rich repertoire of ion channels, including calcium, chloride and potassium channels, as well as gap junction (intercellular) channels. Among these, the K(ATP) (i.e., the metabolically regulated K(+) channel) and the K(Ca) (i.e., maxi-K or large conductance, calcium-sensitive K(+) channel) nonjunctional channel subtypes, as well as connexin43-derived gap junction (intercellular) channels, are thought to be particularly relevant to the control of corporal myocyte contractility. In fact, whereas K(+) channels are an important convergence point for modulating cellular function, gap junctions are a major conduit for ensuring coordinated cellular, and thus tissue, function. The evidence documenting the presence and physiological relevance of K(+) channels and gap junctions to human erectile physiology and function is reviewed. Finally, one potentially revolutionary therapeutic strategy that takes advantage of the important contribution of K(+) channels and gap junctions to erectile physiology is described: maxi-K ion channel (gene) therapy.
阴茎海绵体和动脉平滑肌细胞(肌细胞)收缩状态(即收缩和舒张)的变化控制着进出阴茎的血流,因此最终对勃起能力有重大影响。与许多其他类型的平滑肌细胞一样,海绵体肌细胞的收缩性与离子通道活性密切相关。海绵体平滑肌细胞拥有丰富的离子通道种类,包括钙通道、氯通道和钾通道,以及缝隙连接(细胞间)通道。其中,K(ATP)(即代谢调节性钾通道)和K(Ca)(即大电导钙激活钾通道)非连接通道亚型,以及连接蛋白43衍生的缝隙连接(细胞间)通道,被认为与海绵体肌细胞收缩性的控制特别相关。事实上,钾通道是调节细胞功能的重要汇聚点,而缝隙连接是确保细胞乃至组织功能协调的主要途径。本文综述了关于钾通道和缝隙连接在人类勃起生理和功能中的存在及其生理相关性的证据。最后,描述了一种利用钾通道和缝隙连接对勃起生理的重要贡献的潜在革命性治疗策略:大电导钙激活钾通道(基因)治疗。