Permeation properties of the hair cell mechanotransducer channel provide insight into its molecular structure

Pan B, Waguespack J, Schnee ME, LeBlanc C, Ricci AJ. Permeation properties of the hair cell mechanotransducer channel provide insight into its molecular structure. J Neurophysiol 107: 2408-2420, 2012. First published February 8, 2012; doi:10.1152/jn.01178.2011.-Mechanoelectric transducer (MET) channels, located near stereocilia tips, are opened by deflecting the hair bundle of sensory hair cells. Defects in this process result in deafness. Despite this critical function, the molecular identity of MET channels remains a mystery. Inherent channel properties, particularly those associated with permeation, provide the backbone for the molecular identification of ion channels. Here, a novel channel rectification mechanism is identified, resulting in a reduced pore size at positive potentials. The apparent difference in pore dimensions results from Ca2+ binding within the pore, occluding permeation. Driving force for permeation at hyperpolarized potentials is increased because Ca2+ can more easily be removed from binding within the pore due to the presence of an electronegative external vestibule that dehydrates and concentrates permeating ions. Alterations in Ca2+ binding may underlie tonotopic and Ca2+-dependent variations in channel conductance. This Ca2+-dependent rectification provides targets for identifying the molecular components of the MET channel.