At the synapse between olivocochlear efferent fibers and outer hair cells (
OHCs) of the cochlea, a non-classical ionotropic cholinergic receptor allow
s Ca2+ entry into the hair cell, thus activating a Ca2+-sensitive K+ curren
t which hyperpolarizes the cell's membrane. In the mammalian ear, this lead
s to a reduction in basilar membrane motion, altering auditory nerve fiber
activity and reducing the dynamic range of hearing. The alpha 9 nicotinic a
cetylcholine receptor (nAChR) subunit mediates synaptic transmission betwee
n cholinergic olivocochlear fibers and OHCs. Given that Ca2+ is a key playe
r at this inhibitory synapse, we evaluated the permeability to Ca2+ of the
recombinant a9 receptor expressed in Xenopus laevis oocytes and the modulat
ion of its activity by extracellular Ca2+. Our results show that the a9 rec
eptor is highly permeable to Ca2+ and that this cation potently blocks mono
valent currents through this channel (IC50 = 100 mu M, at -70 mV) in a volt
age-dependent manner. At a Ca2+ concentration similar to that found in the
perilymph bathing the base of the OHCs, approximately 90% of the Na+ curren
t 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.