Direct measurement of the action of acetylcholine on isolated outer hair cells of the guinea pig cochlea

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Abstract
Acetylcholine has long been thought to be the neurotransmitter of the cochlear efferent system in mammals although the evidence is largely indirect. By using whole-cell recordings from isolated outer hair cells, we show that acetylcholine activates a large rapidly desensitizing outward potassium current. This corresponds to hyperpolarization of the membrane potential from rest. The half maximal dose for acetylcholine was 13.5 $\mu $M with a cooperativity of 2. The response was not due to a conventional muscarinic action of acetylcholine for it was not blocked by 0.1 $\mu $M atropine and muscarinic antagonists but it could be blocked by 0.1 $\mu $M curare, suggesting that it shared many properties of a nicotinic receptor. It was, however, inhibited by 10 $\mu $M strychnine. The potassium current activated by acetylcholine required external calcium and was characterized by a significant delay at room temperature. This points to the involvement of a second messenger system, possibly calcium itself.