Impact of arrhythmogenic calmodulin variants on small conductance Ca2+‐activated K+ (SK3) channels

  title={Impact of arrhythmogenic calmodulin variants on small conductance Ca2+‐activated K+ (SK3) channels},
  author={Arnela Saljic and Kalai Mangai Muthukumarasamy and Jonas M. la Cour and Kim Boddum and Morten Grunnet and Martin W Berchtold and Thomas Jespersen},
  journal={Physiological Reports},
Calmodulin (CaM) is a ubiquitous Ca2+‐sensing protein regulating many important cellular processes. Several CaM‐associated variants have been identified in a small group of patients with cardiac arrhythmias. The mechanism remains largely unknown, even though a number of ion channels, including the ryanodine receptors and the L‐type calcium channels have been shown to be functionally affected by the presence of mutant CaM. CaM is constitutively bound to the SK channel, which underlies the… Expand
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Using a rat model of cardiac hypertrophy induced by thoracic aortic banding, it is found that functional upregulation of SK2 channels in hypertrophic rat ventricular cardiomyocytes is driven by protein kinase A (PKA) phosphorylation. Expand
Small Conductance Ca2+-activated K+ Channels and Calmodulin
Ca2+-independent interactions with CaM are required for surface expression of SK channels, whereas the constitutive association between the two channel subunits is not an essential requirement for gating. Expand
Arrhythmogenic Calmodulin Mutations Disrupt Intracellular Cardiomyocyte Ca2+ Regulation by Distinct Mechanisms
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Critical roles of a small conductance Ca²⁺-activated K⁺ channel (SK3) in the repolarization process of atrial myocytes.
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Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease.
These findings suggest that the clinical presentation of CPVT or LQTS associated with these five CaM mutations may involve both altered intrinsic Ca(2+)-binding as well as defective interaction with RyR2. Expand
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