TY - JOUR T1 - Vestibular Hair Bundles Control pH with (Na<sup>+</sup>, K<sup>+</sup>)/H<sup>+</sup> Exchangers NHE6 and NHE9 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9944 LP - 9955 DO - 10.1523/JNEUROSCI.2990-06.2006 VL - 26 IS - 39 AU - Jennifer K. Hill AU - Christopher L. Brett AU - Anthony Chyou AU - Laura M. Kallay AU - Masao Sakaguchi AU - Rajini Rao AU - Peter G. Gillespie Y1 - 2006/09/27 UR - http://www.jneurosci.org/content/26/39/9944.abstract N2 - In hair cells of the inner ear, robust Ca2+/H+ exchange mediated by plasma-membrane Ca2+-ATPase would rapidly acidify mechanically sensitive hair bundles without efficient removal of H+. We found that, whereas the basolateral membrane of vestibular hair cells from the frog saccule extrudes H+ via an Na+-dependent mechanism, bundles rapidly remove H+ in the absence of Na+ and HCO3−, even when the soma is acidified. K+ was fully effective and sufficient for H+ removal; in contrast, Rb+ failed to support pH recovery. Na+/H+-exchanger isoform 1 (NHE1) was present on hair-cell soma membranes and was likely responsible for Na+-dependent H+ extrusion. NHE6 and NHE9 are organellar isoforms that can appear transiently on plasma membranes and have been proposed to mediate K+/H+ exchange. We identified NHE6 in a subset of hair bundles; NHE9 was present in all bundles. Heterologous expression of these isoforms in yeast strains lacking endogenous exchangers conferred pH-dependent tolerance to high levels of KCl and NaCl. NHE9 preferred cations in the order K+, Na+ ≫ Rb+, consistent with the relative efficacies of these ions in promoting pH recovery in hair bundles. Electroneutral K+/H+ exchange, which we propose is performed by NHE9 in hair bundles, exploits the high-K+ endolymph, responds only to pH imbalance across the bundle membrane, is unaffected by the +80 mV endocochlear potential, and uses mechanisms already present in the ear for K+ recycling. This mechanism allows the hair cell to remove H+ generated by Ca2+ pumping without ATP hydrolysis in the cell. ER -