TY - JOUR
T1 - Calmodulin kinase and L-type calcium channels
T2 - A recipe for arrhythmias?
AU - Anderson, Mark E.
N1 - Funding Information:
This work was possible due to the collaborative efforts of a number of gifted scientists. Special thanks are due to Drs. Andy Braun, Roger Colbran, Igor Dzhura, Dan Roden, Howard Schulman, Yuejin Wu, and Rong Zhang. Ms. Linda Selfridge provided excellent secretarial assistance. M.E.A. is an established investigator of the American Heart Association and receives funding from the National Institutes of Health (HL62494, HL70250, and HL46681).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2004/5
Y1 - 2004/5
N2 - L-type Ca2+ channels (LTCCs) are the main portal for Ca 2+ entry into cardiac myocytes. These ion channel proteins open in response to cell membrane depolarizations elicited by action potentials, and LTCC current (ICa) flows during the action potential plateau, to increase cellular Ca2+ (Ca2+ i) and trigger myocardial contraction. ICa is also implicated in the genesis of cardiac arrhythmias under conditions such as heart failure and cardiac hypertrophy, in which the action potential plateau and QT interval are prolonged. This article reviews recent findings about the molecular regulation of LTCCs by the Ca2+-dependent signaling molecule, calmodulin kinase II (CaMKII), and compares this form of regulation with regulation by calmodulin-binding domains and β-adrenergic receptor agonists. LTCC dysregulation is discussed in the context of new results showing that CaMKII can be a proarrhythmic signal in disease conditions in which Ca2+ i is disordered and cardiac repolarization is excessively prolonged.
AB - L-type Ca2+ channels (LTCCs) are the main portal for Ca 2+ entry into cardiac myocytes. These ion channel proteins open in response to cell membrane depolarizations elicited by action potentials, and LTCC current (ICa) flows during the action potential plateau, to increase cellular Ca2+ (Ca2+ i) and trigger myocardial contraction. ICa is also implicated in the genesis of cardiac arrhythmias under conditions such as heart failure and cardiac hypertrophy, in which the action potential plateau and QT interval are prolonged. This article reviews recent findings about the molecular regulation of LTCCs by the Ca2+-dependent signaling molecule, calmodulin kinase II (CaMKII), and compares this form of regulation with regulation by calmodulin-binding domains and β-adrenergic receptor agonists. LTCC dysregulation is discussed in the context of new results showing that CaMKII can be a proarrhythmic signal in disease conditions in which Ca2+ i is disordered and cardiac repolarization is excessively prolonged.
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U2 - 10.1016/j.tcm.2004.02.005
DO - 10.1016/j.tcm.2004.02.005
M3 - Review article
C2 - 15177266
AN - SCOPUS:2942596098
SN - 1050-1738
VL - 14
SP - 152
EP - 161
JO - Trends in Cardiovascular Medicine
JF - Trends in Cardiovascular Medicine
IS - 4
ER -