Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels

Cell. 2000 Jul 7;102(1):89-97. doi: 10.1016/s0092-8674(00)00013-1.


Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha1D subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their relative contribution to total L-type Ca2+ currents and their physiological role and significance as a drug target remain unknown. Therefore, we generated D-LTCC deficient mice (alpha1D-/-) that were viable with no major disturbances of glucose metabolism. alpha1D-/-mice were deaf due to the complete absence of L-type currents in cochlear inner hair cells and degeneration of outer and inner hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha1D-/- mice. We conclude that alpha1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / physiology*
  • Deafness / congenital*
  • Deafness / etiology
  • Electroencephalography
  • Electrophysiology
  • Hair Cells, Auditory, Inner / physiology
  • Hair Cells, Auditory, Outer / physiology
  • Heart / physiopathology
  • Heart Atria / metabolism
  • Heart Atria / physiopathology
  • Mice
  • Mice, Knockout
  • Rabbits
  • Sinoatrial Node / physiopathology*


  • Calcium Channels, L-Type