DIRECT MEASUREMENT OF THE ACTION OF ACETYLCHOLINE ON ISOLATED OUTER HAIR-CELLS OF THE GUINEA-PIG COCHLEA

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.