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

Authors: J Platzer, J Engel, A Schrott-Fischer, K Stephan, S Bova, H Chen, H Zheng, J Striessnig

Journal, date & volume: Cell, 2000 Jul 7 , 102, 89-97

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10929716

Abstract
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.