4.4 Review

Review Article Ca2+-dependent modulation of voltage-gated myocyte sodium channels

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Structural basis of cytoplasmic NaV1.5 and NaV1.4 regulation

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Summary: This review focuses on the structural insights into the cytoplasmic C-terminal regulation of Na(V)1.4 and Na(V)1.5, with special attention to Ca2+ sensing by calmodulin, implications for disease, and putative channel dimerization. The determination of eukaryotic Na(V)s structures by cryo-electron microscopy has provided new perspectives on the study of the channels, highlighting the complementary nature of techniques and the intricate cellular mechanisms that modulate these channels.

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Summary: The skeletal muscle Na+ channels can be regulated by changes in intracellular calcium levels, which may affect Na(v)1.4 function. CPA, through a different mechanism, has been shown to increase Na+ channel activity by depleting SR calcium stores. These findings suggest a complex interplay between calcium signaling and Na+ channel regulation in skeletal muscle cells.

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Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation

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Acute atrial arrhythmogenicity and altered Ca2+ homeostasis in murine RyR2-P2328S hearts

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Epac activation, altered calcium homeostasis and ventricular arrhythmogenesis in the murine heart

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