Voltage gated calcium channels are essential for cardiac physiology by serving as sarcolemma-
restricted gatekeepers for calcium in cardiac myocytes. Activation of the L-type voltagegated
calcium channel provides the calcium entry required for excitation-contraction coupling and contributes
to the plateau phase of the cardiac action potential. Given these critical physiological roles,
subtle disturbances in L-type channel function can lead to fatal cardiac arrhythmias. Indeed, numerous
human arrhythmia syndromes have been linked to mutations in the L-type channel leading to gain-of-function or loss-offunction
mutations. In this review, we discuss the current state of knowledge regarding these mutations present in Timothy
Syndrome, Long and Short QT Syndromes, Brugada Syndrome and Early Repolarization Syndrome. We discuss the
pathological consequences of the mutations, the biophysical effects of the mutations on the channel as well as possible
therapeutic considerations and challenges for future studies.
Keywords: J Wave syndromes, Timothy syndrome, Brugada syndrome, Early Repolarization syndrome.
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