Cell
Volume 102, Issue 1, 7 July 2000, Pages 89-97
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Article
Congenital Deafness and Sinoatrial Node Dysfunction in Mice Lacking Class D L-Type Ca2+ Channels

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Abstract

Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming α1D 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 (α1D−/−) that were viable with no major disturbances of glucose metabolism. α1D−/− 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 α1D−/− mice. We conclude that α1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.

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