CHOLINERGIC MODULATION OF EXTRACELLULAR ATP-INDUCED CYTOPLASMIC CALCIUM CONCENTRATIONS IN COCHLEAR OUTER HAIR-CELLS

Outer hair cells (OHC) of the mammalian cochlea modulate the inner hai r cell (IHC) mechanoelectrical transduction of sound. They are contact ed by synapsing efferent neurons from the CNS, their main efferent neu rotransmitter being acetylcholine (ACh). OHC function and in particula r their control of [Ca2+](i) is highly important and is modulated by A Ch and also by other substances including extracellular (EC) ATP. OHC carry at their efferent synapse a not yet completely identified neuron al type of ionotropic ACh receptor (AChR), with an unusual pharmacolog y, which is, in vivo and in vitro, reversibly blocked by alpha-bungaro toxin (alpha-bgtx). The AChR mediates a fast influx of Ca2+ into OHC w hich, in turn, activates a closeby located outwardly-directed C-a2+-de pendent K+-channel, thus shortly hyperpolarizing the cell. A cloned ho momeric alpha 9 nAChR mimicks the function and pharmacology of this re ceptor. We here report results from a study designed to observe only s lower effects triggered by EC ATP and the ACh-AChR system. EC presence of ATP at OHC increases [Ca2+](i) by activating both P-2x and P-2y pu rinoceptors and also by indirect activation of OHC L-type Ca2+-channel s. The L-type channel activation is responsible for a large part of th e [Ca2+]i increase. Simultaneous EC presence of ACh and ATP at OHC was found to depress ATP-induced effects on OHC [Ca2+](i), an effect that is completely blocked in the presence of alpha-bgtx. Our observations suggest that the ACh-AChR system is involved in the modulation of the observed EC ATP-triggered events; possibly the OHC AChR is able to ac t both in its well known rapid ionotropic way, but also, perhaps after modification in a slower, metabotropic way interfering with the EC AT P-induced [Ca2+](i) increase. ((C) Elsevier, Paris).