Reddy M M, Bell C L
Division of Biomedical Sciences, University of California, Riverside 92521, USA.
Am J Physiol. 1996 Aug;271(2 Pt 1):C486-94. doi: 10.1152/ajpcell.1996.271.2.C486.
The cholinergic and beta-adrenergic sweat secretions from human sweat glands differ with respect to secretory rates and their susceptibility to cystic fibrosis (CF). Using the cultured beta-adrenergic-sensitive sweat secretory cell, we sought to determine the intracellular electrophysiological mechanisms underlying these functional differences. We found that the cholinergic agonist methacholine (10(-6) M) induced a Ca(2+)-dependent biphasic membrane potential (Vm) response: an initial hyperpolarization and a secondary depolarization. The initial hyperpolarization was independent of bath Cl- and dependent on transmembrane K+ gradient. However, the secondary depolarization of Vm was dependent on bath Cl-. In contrast, the beta-adrenergic agonist isoproterenol (10(-5) M) induced a monophasic depolarization of Vm. This depolarization was 1) dependent on bath Cl-, 2) independent of K+ conductance (GK) blocker Ba2+ (5mM), 3) unaffected by the methacholine-induced secondary depolarization of Vm, and 4) absent in cells derived from CF subjects. These results indicated that the cholinergic agonist-induced secretion mainly involves the activation of Ca(2+)-dependent GK and Cl- conductance (GCl), whereas the beta-adrenergic secretion seems to mainly depend on the activation of cystic fibrosis transmembrane conductance regulator-GCl.
人汗腺的胆碱能和β-肾上腺素能汗液分泌在分泌速率及其对囊性纤维化(CF)的易感性方面存在差异。利用培养的β-肾上腺素能敏感汗液分泌细胞,我们试图确定这些功能差异背后的细胞内电生理机制。我们发现胆碱能激动剂乙酰甲胆碱(10^(-6) M)诱导了一种Ca(2+)依赖性双相膜电位(Vm)反应:初始超极化和继发去极化。初始超极化独立于浴液中的Cl-,并依赖于跨膜K+梯度。然而,Vm的继发去极化依赖于浴液中的Cl-。相比之下,β-肾上腺素能激动剂异丙肾上腺素(10^(-5) M)诱导了Vm的单相去极化。这种去极化1)依赖于浴液中的Cl-,2)独立于K+电导(GK)阻滞剂Ba2+(5mM),3)不受乙酰甲胆碱诱导的Vm继发去极化的影响,4)在CF患者来源的细胞中不存在。这些结果表明,胆碱能激动剂诱导的分泌主要涉及Ca(2+)依赖性GK和Cl-电导(GCl)的激活,而β-肾上腺素能分泌似乎主要依赖于囊性纤维化跨膜电导调节因子-GCl的激活。