Fan S F, Brink P R, Melman A, Christ G J
Department of Urology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York 10461.
J Urol. 1995 Mar;153(3 Pt 1):818-25.
Previous studies have demonstrated that cultured corporal smooth muscle cells have prominent outward K currents composed of several different K channel subtypes. The goals of the present investigation were (1) to assert the nature of these channels and to evaluate the characteristics of the most predominant of these channel subtypes, the Maxi-K+ (KCa) channel, and (2) to compare KCa channel behavior in cultured corporal smooth muscle cells derived from the human corpus cavernosum of two distinct patient populations. The patient population was subdivided into two broad diagnostic categories: Group 1: 4 patients without evidence of organic disease of the corpus cavernosum, 3 of whom had documented erections; and Group 2: 4 patients with organic erectile dysfunction. Consistent with previous observations, 3 different K channel subtypes were detected in both patient populations, with corresponding conductances of 180, 100 and 40 pS, respectively. The approximately 183 pS channel was identified as the KCa channel based on its selective permeability to K+ and the fact that its open probability was modulated by both membrane potential and intracellular calcium levels. Specifically, the relative permeability of the 183 pS KCa channel to K+, Rb+, and NH4+ was 1.00:0.64:0.46. The channel was virtually impermeable to Na+ and Li+ (relative permeability < 0.02). In addition, the KCa channel was responsible for more than 90% of the outward K+ current passed through the cell membrane when depolarized. Furthermore, pharmacological studies using the K channel blocker tetraethylammonium ion (TEA) revealed that the sensitivity of KCa channels to TEA inhibition (as judged by the [TEA] required to block one-half of the outward whole cell current induced by a 90 mV depolarizing pulse) in cells from Group 1 patients was 1.05 +/- 0.22 mM. (n = 10 cells), while in sharp contrast the observed value for cells from Group 2 patients was 12.7 +/- 3.8 (n = 9 cells). The difference between the two groups was highly significant. These observations confirm and extend our previous studies to suggest that the KCa channel plays an important role in corporal smooth muscle physiology and, moreover, that alterations in the function/regulation of KCa channels may be an important feature of organic erectile dysfunction. As such, altered KCa channel behavior may contribute to an impaired hyperpolarizing ability of corporal smooth muscle, possibly altering intracellular calcium homeostasis and, perhaps, corporal smooth muscle reactivity and tone.
以往研究表明，培养的海绵体平滑肌细胞具有由几种不同钾通道亚型组成的显著外向钾电流。本研究的目的是：（1）确定这些通道的性质，并评估这些通道亚型中最主要的大电导钙激活钾通道（KCa）的特性；（2）比较来自两个不同患者群体的人海绵体培养的海绵体平滑肌细胞中KCa通道的行为。患者群体被分为两个大致的诊断类别：第1组：4例无海绵体器质性疾病证据的患者，其中3例有记录的勃起功能；第2组：4例器质性勃起功能障碍患者。与以往观察结果一致，在两个患者群体中均检测到3种不同的钾通道亚型，其相应电导分别为180、100和40 pS。基于其对K+的选择性通透性以及其开放概率受膜电位和细胞内钙水平调节这一事实，将约183 pS的通道鉴定为KCa通道。具体而言，183 pS KCa通道对K+、Rb+和NH4+的相对通透性为1.00:0.64:0.46。该通道对Na+和Li+几乎不通透（相对通透性<0.02）。此外，当细胞去极化时，KCa通道介导了超过90%的通过细胞膜的外向K+电流。此外，使用钾通道阻滞剂四乙铵离子（TEA）的药理学研究表明，第1组患者细胞中KCa通道对TEA抑制的敏感性（通过阻断由90 mV去极化脉冲诱导的外向全细胞电流的一半所需的[TEA]来判断）为1.05±0.22 mM（n = 10个细胞），而与之形成鲜明对比的是，第2组患者细胞的观察值为12.7±3.8（n = 9个细胞）。两组之间的差异非常显著。这些观察结果证实并扩展了我们之前的研究，表明KCa通道在海绵体平滑肌生理学中起重要作用，此外，KCa通道功能/调节的改变可能是器质性勃起功能障碍的一个重要特征。因此，KCa通道行为的改变可能导致海绵体平滑肌超极化能力受损，可能改变细胞内钙稳态，也许还会改变海绵体平滑肌反应性和张力。
