Separate agonist-specific oscillatory mechanisms in cultured human sweat duct cells

1. Cultured sweat duct cells (CSDCs) were grown to confluency on a permeable support, and the pharmacological ion transport regulation was assayed by transepithelial voltage clamp techniques. 2. Exposure of the serosal membrane of CSDCs to methacholine (MCh), lysylbradykinin (LBK) or histamine produced an oscillating short-circuit current (Iscc) response, which could be divided in an initial transient phase and a sustained oscillating phase, the latter of which was totally dependent on external Ca2+. 3. The Iscc responses evoked by LBK and histamine were, in contrast to the cholinergic response, characterized by a marked desensitization and short duration of the subsequent phase of Iscc oscillations. 4. Prolonged Iscc oscillations, reflecting continuous Ca2+ influx, were seen following MCh stimulation, and in response to LBK or histamine stimulation, when cells had been pre-treated with MCh. This pre-treatment effect of MCh was independent of continuous muscarinic receptor occupation, and it was unrelated to nicotinic receptor occupation. 5. It is suggested that MCh stimulation selectively initiates an influx of Ca2+ to an intracellular pool, from where Ca2+ can be discharged repetitively. In contrast, LBK and histamine only activate discharge of Ca2+ from such an intracellular pool, resulting in a limited response, given no prior stimulation by MCh of the Ca2+ influx mechanism.