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Ba2+ currents in inner and outer hair cells of mice lacking the voltage-dependent Ca2+ channel subunits beta3 or

Stephanie Kuhn1, Martina Knirsch, Lukas Rüttiger

  • 1Institute of Physiology II and Department of Otorhinolaryngology, Molecular Neurobiology, University of Tübingen, Tübingen Hearing Research Centre, Tübingen, Germany.

Channels (Austin, Tex.)
|September 17, 2009
PubMed

Insights

Calcium channel auxiliary CaVbeta subunits CaVbeta3 and CaVbeta4 influence hair cell function. While not essential, they modulate Ca2+ channel properties in inner and outer hair cells, impacting hearing.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Auditory Physiology

Background:

  • Voltage-gated calcium channels (CaV) are crucial for cellular functions, composed of pore-forming CaVα1 and auxiliary subunits like CaVβ.
  • CaVβ subunits modulate CaV channel trafficking, surface expression, and biophysical properties.
  • The specific CaVβ subunits associated with CaV1.3 channels in cochlear hair cells, vital for synaptic transmission, remain largely unknown.

Purpose of the Study:

  • To investigate the roles of CaVβ3 and CaVβ4 auxiliary subunits in cochlear hair cells (inner hair cells - IHCs and outer hair cells - OHCs).
  • To determine the contribution of CaVβ3 and CaVβ4 to the biophysical properties of Ca2+ currents in IHCs and OHCs.

Main Methods:

  • Analysis of CaVβ3 knockout (CaVβ3(-/-)) and CaVβ4 mutant (CaVβ4(lh/lh)) mice with normal hearing.
  • Recording of voltage-activated Ba2+ currents in hair cells from these mouse models and their wild-type controls.
  • Comparison of cell size, current amplitudes, voltage dependence, and kinetics of Ba2+ currents between mutant and wild-type hair cells.

Main Results:

  • CaVβ4 was detected in IHCs, as neonatal CaVβ4(lh/lh) IHCs exhibited reduced membrane capacitance, altered current activation kinetics and voltage dependence, and mature IHCs showed reduced peak currents.
  • CaVβ3 was implicated in OHC function, as CaVβ3(-/-) OHCs displayed significantly reduced Ba2+ current amplitudes, altered activation kinetics and voltage dependence, and increased inactivation.
  • Neither CaVβ3 nor CaVβ4 proved indispensable for hair cell Ca2+ currents, but both significantly contributed to their overall properties.

Conclusions:

  • CaVβ4 plays a role in modulating Ca2+ channel function in inner hair cells.
  • CaVβ3 is important for the proper functioning of outer hair cells.
  • These auxiliary subunits fine-tune Ca2+ channel activity in cochlear hair cells, contributing to auditory function.

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Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
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The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.