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

599Citations
Citations of this article
189Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Platzer, J., Engel, J., Schrott-Fischer, A., Stephan, K., Bova, S., Chen, H., … Striessnig, J. (2000). Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell, 102(1), 89–97. https://doi.org/10.1016/S0092-8674(00)00013-1

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free