Calmodulin kinase and L-type calcium channels; a recipe for arrhythmias?
M. Anderson. Trends Cardiovasc. Med.14
152--161 (May 2004)
L-type Ca$^2+$ 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 (I(Ca)) flows during the action potential plateau, to
increase cellular Ca$^2+$ (Ca$^2+$(i)) and trigger myocardial
contraction. I(Ca) 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 Ca$^2+$-dependent signaling molecule, calmodulin
kinase II (CaMKII), and compares this form of regulation with regulation
by calmodulin-binding domains and beta-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 Ca$^2+$(i) is disordered and cardiac repolarization is