CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells

J Neurosci. 2003 Nov 26;23(34):10832-40. doi: 10.1523/JNEUROSCI.23-34-10832.2003.

Abstract

Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. During early development, afferent synaptic transmission is triggered by spontaneous Ca2+ spikes of IHCs, which are under efferent cholinergic control. Around the onset of hearing, large-conductance Ca2+-activated K+ channels are acquired, and Ca2+ spikes as well as the cholinergic innervation are lost. Here, we performed patch-clamp measurements in IHCs of mice lacking the CaV1.3 channel (CaV1.3-/-) to investigate the role of this prevailing voltage-gated Ca2+ channel in IHC development and synaptic function. The small Ca2+ current remaining in IHCs from 3-week-old CaV1.3-/- mice was mainly mediated by L-type Ca2+ channels, because it was sensitive to dihydropyridines but resistant to inhibitors of non-L-type Ca2+ channels such as omega-conotoxins GVIA and MVIIC and SNX-482. Depolarization induced only marginal exocytosis in CaV1.3-/- IHC, which was solely mediated by L-type Ca2+ channels, whereas robust exocytic responses were elicited by photolysis of caged Ca2+. Secretion triggered by short depolarizations was reduced proportionally to the Ca2+ current, suggesting that the coupling of the remaining channels to exocytosis was unchanged. CaV1.3-/- IHCs lacked the Ca2+ action potentials and displayed a complex developmental failure. Most strikingly, we observed a continued presence of efferent cholinergic synaptic transmission and a lack of functional large-conductance Ca2+-activated K+ channels up to 4 weeks after birth. We conclude that CaV1.3 channels are essential for normal hair cell development and synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / deficiency*
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Cell Separation
  • Cochlea / cytology*
  • Cochlea / physiology*
  • Deafness / genetics
  • Electric Capacitance
  • Exocytosis / physiology
  • Hair Cells, Auditory, Inner / cytology
  • Hair Cells, Auditory, Inner / metabolism*
  • Large-Conductance Calcium-Activated Potassium Channels
  • Membrane Potentials / physiology
  • Mice
  • Mice, Knockout
  • Patch-Clamp Techniques
  • Potassium Channels, Calcium-Activated / metabolism

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Calcium