Localisation of SCN10A Gene Product Nav1.8 and Novel Pain-Related Ion Channels in Human Heart

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We have shown that the gene SCN10A encoding the sodium channel Nav1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Nav1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Nav1.8 and other key nociceptive ion channels, including Nav1.7, Nav1.9, capsaicin receptor TRPV1, and purinergic receptor P2X3, have not been reported in human heart. The aim of this study was to determine the distribution of Nav1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Nav1.8 and other markers. Nav1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Nav1.8 nerve fibres per mm2 correlated significantly with vascular markers. Nav1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Nav1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Nav1.7, Nav1.9, TRPV1, P2X3/P2X2, and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Nav1.8 is present in sensory nerves and cardiomyocytes of human heart. Nav1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

Localisation of SCN10A Gene Product Nav1.8 and Novel Pain-Related Ion Channels in Human Heart

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