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The Journal of Neuroscience, July 15, 2001, 21(14):5066-5078

Plasma Membrane Ca²⁺-ATPase Isoform 2a Is the PMCA of Hair Bundles

Rachel A. Dumont^{1, 2}, Ulysses Lins⁴, Adelaida G. Filoteo⁵, John T. Penniston⁵, Bechara Kachar⁴, and Peter G. Gillespie^{2, 3}

¹ Department of Physiology, Johns Hopkins University, Baltimore, Maryland 21205, ² Oregon Hearing Research Center and ³ Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, ⁴ Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, and ⁵ Department of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905

Mechanoelectrical transduction channels of hair cells allow for the entry of appreciable amounts of Ca²⁺, which regulates adaptation and triggers the mechanical activity of hair bundles. Most Ca²⁺ that enters transduction channels is extruded by the plasma membrane Ca²⁺-ATPase (PMCA), a Ca²⁺ pump that is highly concentrated in hair bundles and may be essential for normal hair cell function. Because PMCA isozymes and splice forms are regulated differentially and have distinct biochemical properties, we determined the identity of hair bundle PMCA in frog and rat hair cells. By screening a bullfrog saccular cDNA library, we identified abundant PMCA1b and PMCA2a clones as well as rare PMCA2b and PMCA2c clones. Using immunocytochemistry and immunoprecipitation experiments, we showed in bullfrog sacculus that PMCA1b is the major isozyme of hair cell and supporting cell basolateral membranes and that PMCA2a is the only PMCA present in hair bundles. This complete segregation of PMCA1 and PMCA2 isozymes holds for rat auditory and vestibular hair cells; PMCA2a is the only PMCA isoform in hair bundles of outer hair cells and vestibular hair cells and is the predominant PMCA of hair bundles of inner hair cells. Our data suggest that hair cells control plasma membrane Ca²⁺-pumping activity by targeting specific PMCA isozymes to distinct subcellular locations. Because PMCA2a is the only Ca²⁺ pump present at appreciable levels in hair bundles, the biochemical properties of this pump must account fully for the physiological features of transmembrane Ca²⁺ pumping in bundles.

Key words: hair cells; stereocilia; cochlea; calcium; calcium pump; isozymes

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21145066-13$05.00/0

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