Distinct cellular mechanisms of cholinergic and beta-adrenergic sweat secretion.
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.
Reddy
M M
MM
Division of Biomedical Sciences, University of California, Riverside 92521, USA.
Bell
C L
CL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology; D018678:Cholinergic Agents / Q000494:pharmacology*; D004553:Electric Conductivity; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D013542:Sweat / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002712:Chlorides; D018678:Cholinergic Agents; D016210:Methacholine Chloride; D007545:Isoproterenol; D011188:Potassium