Effects of ammonium chloride on membrane currents of acinar cells dispersed from the rat parotid gland

In acinar cells freshly dispersed from rat parotid glands, the effects of ammonium chloride (NH4Cl) on membrane currents were studied using the whole-cell clamp method. When membrane currents were recorded with command pulses to 0 mV, applied at 2-s intervals from a holding potential of −70 mV, NH4Cl (5–20 mM) transiently decreased outward currents and then slowly increased both outward and inward currents. After reaching a peak in about 40–50 s, both outward and inward currents gradually decreased in the presence of NH4Cl and, on its wash-out, the currents returned to the control level. Butyrate (5–20 mM) had little effect on the resting membrane currents, but markedly inhibited the response to NH4Cl. Tetraethylammonium (5 mM) strongly reduced both the resting and NH4Cl-induced outward currents, whereas it slightly potentiated the NH4Cl-induced inward current without affecting the membrane current at the holding potential. Without ATP in the patch pipettes, carbachol-induced membrane currents were relatively resistant to Ca2+ removal from the external medium, but NH4Cl-induced currents were quickly abolished in the absence of Ca2+. We conclude that intracellular alkalinization with NH4Cl increases Ca2+ influx and activates Ca2+-dependent outward K+ and inward Cl− currents.