Plasma membrane Ca2+-ATPase extrudes Ca2+ from hair cell stereocilia

Ebenezer N. Yamoah, Ellen A. Lumpkin, Rachel A. Dumont, Peter J.S. Smith, A. J. Hudspeth, Peter G. Gillespie

Research output: Contribution to journalArticlepeer-review

186 Scopus citations

Abstract

Mechanically sensitive hair cells of the auditory and vestibular systems use Ca2+ to control adaptation of mechanical transduction, to effect frequency tuning, to trigger neurotransmitter release, and to mediate efferent synaptic signaling. To determine the role that pumps play in regulation of Ca2+ in the hair bundle, the organelle responsible for mechanoelectrical transduction, we localized and quantified the plasma membrane Ca2+-ATPase (PMCA) of the bundle. We found that each hair bundle contains ~106 PMCA molecules or ~2000 per square micrometer of bundle membrane and that PMCA is the principal calmodulin binding protein of the bundle. Consistent with biochemical estimates of PMCA density, we measured with extracellular Ca2+-selective electrodes a substantial Ca2+ efflux from bundles. The number of bundle Ca2+ pumps and magnitude of resting Ca2+ efflux suggested that PMCA should generate a substantial membrane current as bundles expel Ca2+. Measurement of whole-cell currents revealed a transduction-dependent outward current that was consistent with the activity of PMCA. Finally, dialysis of hair cells with PMCA inhibitors led to a large increase in the concentration of Ca2+ in bundles, which suggests that PMCA plays a major role in regulating bundle Ca2+ concentration. Our data further indicate that PMCA could elevate the extracellular Ca2+ concentration close to hair bundles above the low level found in bulk endolymph.

Original languageEnglish (US)
Pages (from-to)610-624
Number of pages15
JournalJournal of Neuroscience
Volume18
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • ATPase
  • Calcium
  • Hair bundle
  • Hair cell
  • Hearing
  • Ion-selective probe
  • Stereocilia

ASJC Scopus subject areas

  • General Neuroscience

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