Fast Ca2+ signals at mouse inner hair cell synapse: a role for Ca2+ induced Ca2+ release

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Abstract

Inner hair cells of the mammalian cochlea translate acoustic stimuli into 'phase-locked' nerve impulses with frequencies of up to at least 1 kHz. Little is known about the intracellular Ca2+ signal that links transduction to the release of neurotransmitter at the afferent synapse. Here, we use confocal microscopy to provide evidence that Ca2+-induced Ca2+ release (CICR) may contribute to the mechanism. Line scan images (2 ms repetition rate) of neonatal mouse inner hair cells filled with the fluorescent indicator FLUO-3, revealed a transient increase in intracellular Ca2+ concentration ([Ca2+]i) during brief (5-50 ms) depolarizing commands under voltage clamp. The amplitude of the [Ca2+]i transient depended upon the Ca2+ concentration in the bathing medium in the range 0-1.3 mM. [Ca2+]i transients were confined to a region near the plasma membrane at the base of the cell in the vicinity of the afferent synapses. The change in [Ca2+]i appeared uniform throughout the entire basal sub-membrane space and we were unable to observe hotspots of activity. Both the amplitude and the rate of rise of the [Ca2+]i transient was reduced by external ryanodine (20 microM), an agent that blocks Ca2+ release from the endoplasmic reticulum. Intracellular Cs+, commonly used to record at presynaptic sites, produced a similar effect. We conclude that both ryanodine and intracellular Cs+ block CICR in inner hair cells. We discuss the contribution of CICR to the measured [Ca2+]i transient, the implications for synaptic transmission at the afferent synapse and the significance of its sensitivity to intracellular Cs+.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalJournal of Physiology
Volume539
Issue number1
DOIs
Publication statusPublished - 15 Feb 2002

Keywords

  • Animals
  • Calcium
  • Calcium Signaling
  • Cesium
  • Electric Conductivity
  • Hair Cells, Auditory, Inner
  • Mice
  • Mice, Inbred Strains
  • Ryanodine
  • Synapses
  • Time Factors

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