The promiscuous nature of the cardiac sodium current.
Voltage-gated sodium channels (Na(V)s) are essential in propagating neuronal electrical impulse and triggering muscle contraction. In the heart, the Na(+) channel isoform Na(V)1.5 is strongly expressed and in the past was thought to be solely responsible for generating the cardiac Na(+) current (I(Na)). Recent studies, however, revealed that neuronal and skeletal muscle Na(+) channel isoforms are also expressed in the heart and contribute to cardiac I(Na). Amongst the findings is that many neuronal type Na(V)s are expressed in specific areas of the conduction system and ventricles. The contribution of these TTX-sensitive channels to normal cardiac function remains unclear but these data raise the possibility of a more prominent role of TTX-sensitive channels in conduction. Moreover, cardiac arrhythmias are commonly observed in many neuronal and musculoskeletal diseases despite their exclusive linkage to mutations in the neuronal and skeletal muscle sodium channel isoforms. The cause for these arrhythmias remains poorly understood. These recent findings indicate that neuronal and skeletal muscle sodium channels are expressed in areas of the heart that may be involved in the clinical phenotypes observed. The purpose of this review is to give an overview of the evidence for the presence of TTX-sensitive Na(V) isoforms in the heart and present the hypothesis brought forward so far for their direct role in cardiac function. These data demonstrate the promiscuous nature of the cardiac sodium current at the molecular level and should help us to bridge the gap that exists between our understanding of cardiac physiology and arrhythmias associated to brain and myotonic diseases.
Haufe
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Département de Physiologie et Biophysique Faculté de Médecine et Sciences de la Santé, Université de Sherbrooke, 3001 12th Ave. Sherbrooke, Quebec, Canada J1H 5N4.
Chamberland
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C
Dumaine
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R
D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D015222:Sodium Channels; D012964:Sodium