Inhibition of TASK1-like channels by muscarinic receptor stimulation in rat adrenal medullary cells.

The muscarinic receptor is known to be involved in the acetylcholine-induced secretion of catecholamines in the adrenal medulla (AM) cells of various mammals. The ionic mechanisms, however, have not been elucidated yet. Thus, we investigated the issue in acutely isolated rat AM cells with the perforated patch clamp method. Bath application of 30 muM muscarine induced depolarization with the consequent generation of action potentials or an inward current at negative membrane potentials. The muscarine-sensitive current instantaneously changed in amplitude upon application of command pulses without a time-dependent component, altered the polarity as a K(+)-electrode, and showed rectification of the Goldman-Hodgkin-Katz (GHK) type. The whole-cell current at -20 mV was inhibited by external H(+) ions with a concentration responsible for half inhibition of pH 7.09 and muscarine failed to induce a further inward current during exposure to a saline in which pH decreased to 6.5. A similar occlusion occurred in secretion when pH in muscarine-containing saline decreased to 6.6. RT-PCR, immunoblotting, and immunocytochemistry suggested that rat AM cells mainly express the TASK1 channel. This TASK channel in AM cells may directly sense a decrease in blood pH, which occurs during exercise. The muscarine action was mimicked by oxotremorine-methiodide, but not by oxotremorine. The present results indicate that activation of muscarinic receptors or a decrease in external pH in the rat AM cell induces secretion through the inhibition of TASK1-like channels.