High calcium permeability and calcium block of the alpha 9 nicotinic acetylcholine receptor

At the synapse between olivocochlear efferent fibers and outer hair cells (OHCs) of the cochlea, a non-classical ionotropic cholinergic receptor allows Ca2+ entry into the hair cell, thus activating a Ca2+-sensitive K+ current which hyperpolarizes the cell's membrane. In the mammalian ear, this leads to a reduction in basilar membrane motion, altering auditory nerve fiber activity and reducing the dynamic range of hearing. The alpha 9 nicotinic acetylcholine receptor (nAChR) subunit mediates synaptic transmission between cholinergic olivocochlear fibers and OHCs. Given that Ca2+ is a key player at this inhibitory synapse, we evaluated the permeability to Ca2+ of the recombinant a9 receptor expressed in Xenopus laevis oocytes and the modulation of its activity by extracellular Ca2+. Our results show that the a9 receptor is highly permeable to Ca2+ and that this cation potently blocks monovalent currents through this channel (IC50 = 100 mu M, at -70 mV) in a voltage-dependent manner. At a Ca2+ concentration similar to that found in the perilymph bathing the base of the OHCs, approximately 90% of the Na+ current through the alpha 9 receptor is blocked, suggesting that one of the main functions of this channel could be to provide a pathway for Ca2+ influx. (C) 2000 Elsevier Science B.V. All rights reserved.