ACh-evoked complex membrane potential changes in mouse submaxillary gland acini. A study employing channel blockers and atropine.

The responses in membrane potential and resistance of acinar cells to iontophoretically applied acetylcholine (ACh) were investigated using intracellular micro-electrode recording in superfused segments of mouse submaxillary gland. For measurements of membrane resistance and acetylcholine equilibrium potential (EACh), two micro-electrodes were inserted into neighbouring communicating cells. Current could be injected through one of the electrodes. The pattern of membrane potential change induced by ACh depended on the resting potential. Simple hyperpolarizations were induced at low resting potentials, while biphasic potential changes (depolarization followed by hyperpolarization) or simple depolarizations were observed at relatively high resting potentials. A similar dependence of the ACh induced potential change on the resting potential was obtained in experiments in which the resting membrane potential was set at different levels by injecting direct current and stimulating the same cell with equal doses of ACh. The ACh equilibrium potential ranged widely between -45 and -75 mV. Under special conditions the conversion in response to ACh from a hyperpolarization to depolarization could be obtained without change in resting potential. Small doses of ACh evoked simple depolarization, while medium doses induced biphasic responses and large doses of ACh caused hyperpolarization. The effect of a low concentration of atropine on the response was an initial block of hyperpolarization followed by a secondary block of depolarization. Intracellular injection of TEA ions converted the ACh induced potential response from hyperpolarization to depolarization. Both the depolarizing and hyperpolarizing ACh responses were accompanied by a marked reduction in membrane resistance. The depolarization was abolished by a severe reduction in external Na concentration, while the hyperpolarization was sensitive to alternations in external K concentration. These results indicate that some of the complex responses in submaxillary gland acinar cells to ACh may be explained by the interaction between two different kinds of potential change (Na dependent depolarization and K dependent hyperpolarization).