Muscle channelopathies and critical points in functional and genetic studies
Karin Jurkat-Rott, Frank Lehmann-Horn
Karin Jurkat-Rott, Frank Lehmann-Horn
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2000-2009. https://doi.org/10.1172/JCI25525.
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Muscle channelopathies and critical points in functional and genetic studies

Abstract

Muscle channelopathies are caused by mutations in ion channel genes, by antibodies directed against ion channel proteins, or by changes of cell homeostasis leading to aberrant splicing of ion channel RNA or to disturbances of modification and localization of channel proteins. As ion channels constitute one of the only protein families that allow functional examination on the molecular level, expression studies of putative mutations have become standard in confirming that the mutations cause disease. Functional changes may not necessarily prove disease causality of a putative mutation but could be brought about by a polymorphism instead. These problems are addressed, and a more critical evaluation of the underlying genetic data is proposed.

Authors

Karin Jurkat-Rott, Frank Lehmann-Horn

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Figure 1

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Excitation-contraction coupling of skeletal muscle. A muscle fiber is ex...
Excitation-contraction coupling of skeletal muscle. A muscle fiber is excited via the nerve by an endplate potential and generates an action potential, which spreads out along the surface membrane and the transverse tubular system into the deeper parts of the muscle fiber. The dihydropyridine (DHP) receptor senses the membrane depolarization, alters its conformation, and activates the ryanodine receptor, which releases Ca2+ from the SR, a Ca2+ store. Ca2+ binds to troponin and activates the so-called contractile machinery.