DISTINCT CELLULAR MECHANISMS OF CHOLINERGIC AND BETA-ADRENERGIC SWEATSECRETION

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 electr ophysiological mechanisms underlying these functional differences. We found that the cholinergic agonist methacholine (10(-6) M) induced a C a2+-dependent biphasic membrane potential (V-m) response: an initial h yperpolarization and a secondary depolarization. The initial hyper pol arization was independent of bath Cl- and dependent on transmembrane K + gradient. However, the secondary depolarization of V-m was dependent on bath Cl-. In contrast, the beta-adrenergic agonist isoproterenol ( 10(-5) M) induced a monophasic depolarization of V-m. This depolarizat ion was 1) dependent on bath Cl-, 2) independent of K+ conductance (GR ) blocker Ba2+ (5 mM), 3) unaffected by the methacholine-induced secon dary depolarization of V-m, and 4) absent in cells derived from CF sub jects. These results indicated that the cholinergic agonist-induced se cretion mainly involves the activation of Ca2+-dependent G(K) and Cl- conductance (G(Cl)), whereas the beta-adrenergic secretion seems to ma inly depend on. the activation of cystic fibrosis transmembrane conduc tance regulator-G(Cl).