Acetylcholine increases intracellular Ca2+ concentration and hyperpolarizes the guinea-pig outer hair cell

Extracellularly applied acetylcholine (ACh) induced outward currents in isolated outer hair cells of a guinea-pig cochlea. The ACh induced current was carried by K+ ions. The current amplitude was ACh dose dependent with a KD of 12 microM. The ACh induced outward current was reversibly blocked by extracellularly applied atropine (1 microM), d-tubocurarine (d-TC, 1 microM), apamin (1 microM) and strychnine (0.1-10 microM). D-TC (10 microM) not only blocked the ACh induced outward current, but also reduced the amplitude of depolarization induced outward current. ACh induced a rise of intracellular Ca2+ concentration ([Ca2+]i). D-TC (10 microM) reduced but did not totally block the increase of [Ca2+]i. In a low Ca2+ (0.1 mM) extracellular medium, the amplitude of ACh induced current was reduced rapidly and was recovered gradually to the normal level after the extracellular Ca2+ concentration was resumed. It is probable that ACh hyperpolarizes the guinea-pig outer hair cell membrane by activation of a Ca(2+)-activated K+ conductance.