title: Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.
abstract: We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, 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 Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-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. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.
authors.affiliation: Department of Clinical Neuroscience, Hammersmith Hospital, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Facer
authors.forename: Prakash P
authors.initials: PP
authors.lastname: Punjabi
authors.forename: Andleeb
authors.initials: A
authors.lastname: Abrari
authors.forename: Riyaz A
authors.initials: RA
authors.lastname: Kaba
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Severs
authors.forename: John
authors.initials: J
authors.lastname: Chambers
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Kooner
authors.forename: Praveen
authors.initials: P
authors.lastname: Anand
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism / Q000502:physiology
chemical_list: D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D018048:Receptors, Purinergic P2; C568317:SCN10A protein, human; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C076414:SV2A protein, human