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

• Facer Paul

  Department of Clinical Neuroscience, Hammersmith Hospital, Faculty of Medicine, Imperial College London

• Punjabi Prakash P.

  Department of Cardiothoracic Surgery, Hammersmith Hospital, Faculty of Medicine, Imperial College London

• Abrari Andleeb

  Department of Histopathology, Max Super Speciality Hospitals

• Kaba Riyaz A.

  Royal Brompton Hospital, Imperial College London

• Severs Nicholas J.

  Royal Brompton Hospital, Imperial College London

• Chambers John

  Department of Cardiology, Hammersmith Hospital, Faculty of Medicine, Imperial College London

• Kooner Jaspal S.

  Department of Cardiology, Hammersmith Hospital, Faculty of Medicine, Imperial College London

• Anand Praveen

  Department of Clinical Neuroscience, Hammersmith Hospital, Faculty of Medicine, Imperial College London

抄録

We have shown that the gene SCN10A encoding the sodium channel Na_v1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na_v1.8 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_v1.8 and other key nociceptive ion channels, including Na_v1.7, Na_v1.9, 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 Na_v1.8, 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_v1.8 and other markers. Na_v1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na_v1.8 nerve fibres per mm² correlated significantly with vascular markers. Na_v1.8-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_v1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na_v1.7, Na_v1.9, TRPV1, P2X₃/P2X₂, and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na_v1.8 is present in sensory nerves and cardiomyocytes of human heart. Na_v1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

収録刊行物

• International Heart Journal

  International Heart Journal 52 (3), 146-152, 2011

  一般社団法人 インターナショナル・ハート・ジャーナル刊行会

キーワード

• Gene
• Sodium channel
• Cardiac
• Pain
• ECG

詳細情報

• CRID: 1390001205224650752
• NII論文ID: 130000770912
• DOI: 10.1536/ihj.52.146
• ISSN: 13493299
• ISSN: 13492365
• Web Site: http://www.jstage.jst.go.jp/article/ihj/52/3/52_3_146/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012103201
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可