Abstract
QT interval prolongation is incontrovertibly linked to increased risk
of arrhythmias but, paradoxically, QT interval prolongation can also
be an effective antiarrhythmic strategy and is in fact the goal of
class III antiarrhythmic drugs. This discussion examines the cellular
effects of QT interval prolongation and proposes that calmodulin
kinase II (CaMKII) is a specific cellular proarrhythmic signal that
is activated downstream to QT interval prolongation. Inhibition of
CaMKII can prevent cellular arrhythmia surrogates and in vivo arrhythmias
linked to excessive action potential prolongation, suggesting that
QT interval prolongation alone does not fully account for proarrhythmia.
This reasoning points to the conclusion that QT interval modulation
and prolongation not only grades cellular Ca$^2+$ entry for cardiac
contraction but also has the potential to recruit Ca$^2+$-activated
signalling molecules. CaMKII is one of these molecules and CaMKII
activity is at least partially responsible for the proarrhythmic
consequences of excessive QT interval prolongation.
- 16336516
- action
- amp-dependent
- arrhythmia,
- biological,
- calcium
- calcium,
- cardiomyopathies,
- channel,
- channels,
- congestive,
- cyclic
- dependent
- extramural,
- failure,
- gov't,
- heart
- heart,
- homeostasis,
- humans,
- kinase,
- kinases,
- l-type,
- long
- models,
- myocardium,
- n.i.h.,
- non-u.s.
- potentials,
- protein
- qt
- receptor
- release
- research
- reticulum,
- ryanodine
- sarcoplasmic
- support,
- syndrome,
- {c}a$^{2+}$-calmodulin
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