Cholinergic-induced oscillating transepithelial short-circuit current in cultured human sweat duct cells

Human sweat duct cells in primary culture were investigated by voltage-clamp technique. Stimulation with the muscarinic agonist, metacholine (MCh), produced an abrupt transient rise followed by sustained regular oscillations in the transepithelial short-circuit current (Iscc), which in these cells is carried by a mucosal amiloride-sensitive Na+ influx, secondary to a Ca2(+)-activated, voltage-dependent, large K+ shunt across the serosal membrane. The time of latency, the initial transient phase, and the sustained oscillating phase of the MCh-induced Iscc response were demonstrated to be differently affected by changes in temperature, agonist concentration and external Ca2+ supply. From these results a model is proposed for the MCh-induced signal transduction in cultured sweat duct cells, involving a primary intracellular oscillatory Ca2+ mobilization, activated by IPP, sustained by a temperature-regulated external Ca2+ supply, and counter-regulated by cytosolic Ca2+.