Regulation of outer hair cell cytoskeletal stiffness by intracellular Ca2+: Underlying mechanism and implications for cochlear mechanics

Gregory I. Frolenkov, Fabio Mammano, Bechara Kachar

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Two Ca2+-dependent mechanisms have been proposed to regulate the mechanical properties of outer hair cells (OHCs), the sensory-motor receptors of the mammalian cochlea. One involves the efferent neurotransmitter, acetylcholine, decreasing OHC axial stiffness. The other depends on elevation of intracellular free Ca2+ concentration ([Ca2+]i) resulting in OHC elongation, a process known as Ca2+-dependent slow motility. Here we provide evidence that both these phenomena share a common mechanism. In whole-cell patch-clamp conditions, a fast increase of [Ca2+]i by UV-photolysis of caged Ca2+ or by extracellular application of Ca2+ -ionophore, ionomycin, produced relatively slow (time constant ∼ 20 s) cell elongation. When OHCs were partially collapsed by applying minimal negative pressure through the patch pipette, elevation of the [Ca2+]i up to millimole levels (estimated by Fura-2) was unable to restore the cylindrical shape of the OHC. Stiffness measurements with vibrating elastic probes showed that the increase of [Ca2+]i causes a decrease of OHC axial stiffness, with time course similar to that of the Ca2+-dependent elongation, without developing any measurable force. We concluded that, contrary to a previous proposal, Ca2+-induced OHC elongation is unlikely to be driven by circumferential contraction of the lateral wall, but is more likely a passive mechanical reaction of the turgid OHC to Ca2+-induced decrease of axial stiffness. This may be the key phenomenon for controlling gain and operating point of the cochlear amplifier.

Original languageEnglish
Pages (from-to)185-195
Number of pages11
JournalCell Calcium
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2003

Funding

FundersFunder number
National Institute on Deafness and Other Communication DisordersZ01DC000002

    Keywords

    • Acetylcholine
    • Cochlear amplifier
    • Intracellular calcium stores
    • Olivocohlear bundle
    • Prestin
    • Slow motility

    ASJC Scopus subject areas

    • Physiology
    • Molecular Biology
    • Cell Biology

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