Article abstract
Nature Cell Biology 2, 173 - 177 (2000)
Published online: 10 February 2000 | doi:10.1038/35004052
Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels
Igor Dzhura1, Yuejin Wu2, Roger J. Colbran3, Jeffrey R. Balser1,4 & Mark E. Anderson2,4
Abstract
A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for ICa facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent ICa facilitation.
- Department of Anesthesiology, Vanderbilt University, Nashville, Tennessee 37232, USA
- Department of Internal Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
- Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
Correspondence to: Mark E. Anderson2,4 e-mail: mark.anderson@mcmail.vanderbilt.edu
