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

• Published in: Cell calcium (Edinburgh) 2003-03, Vol.33 (3), p.185-195
• Main Authors: Frolenkov, Gregory I, Mammano, Fabio, Kachar, Bechara
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Animals; Calcium - metabolism; Calcium - pharmacology; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cell Size - drug effects; Cell Size - physiology; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Cytoskeleton - ultrastructure; Elasticity - drug effects; Fura-2; Guinea Pigs; Hair Cells, Auditory, Outer - drug effects; Hair Cells, Auditory, Outer - metabolism; Hair Cells, Auditory, Outer - ultrastructure; Hearing - physiology; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; Ionophores - pharmacology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Reaction Time - drug effects; Reaction Time - physiology; Stress, Mechanical; Synaptic Transmission - physiology; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0143-4160
• DOI: 10.1016/S0143-4160(02)00228-2

Two Ca(2+)-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 Ca(2+) concentration ([Ca(2+)](i)) resulting in OHC elongation, a process known as Ca(2+)-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 [Ca(2+)](i) by UV-photolysis of caged Ca(2+) or by extracellular application of Ca(2+)-ionophore, ionomycin, produced relatively slow (time constant approximately 20s) cell elongation. When OHCs were partially collapsed by applying minimal negative pressure through the patch pipette, elevation of the [Ca(2+)](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 [Ca(2+)](i) causes a decrease of OHC axial stiffness, with time course similar to that of the Ca(2+)-dependent elongation, without developing any measurable force. We concluded that, contrary to a previous proposal, Ca(2+)-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 Ca(2+)-induced decrease of axial stiffness. This may be the key phenomenon for controlling gain and operating point of the cochlear amplifier.