HCN-related channelopathies

  • Mirko Baruscotti
  • Georgia Bottelli
  • Raffaella Milanesi
  • Jacopo C. DiFrancesco
  • Dario DiFrancesco
Invited Review

DOI: 10.1007/s00424-010-0810-8

Cite this article as:
Baruscotti, M., Bottelli, G., Milanesi, R. et al. Pflugers Arch - Eur J Physiol (2010) 460: 405. doi:10.1007/s00424-010-0810-8

Abstract

HCN channels are the molecular subunits of native funny (f-) channels of cardiac pacemaker cells and neurons. Although funny channels were first functionally described in cardiac cells in the late 1970s, cloning of HCN channels, of which four subunits are known today (HCN1-4), had to wait some 20 years to be accomplished, which delayed the investigation of HCN-related channelopathies. In cardiac pacemaker cells, the main function of f-channels is to contribute substantially to the generation of spontaneous activity of pacemaker cells and control of heart rate. Given this role in cardiac rhythm, it is natural to expect that defective f-channels (or their molecular correlates HCN4 channels) might be responsible for inheritable forms of cardiac arrhythmogenic diseases. Indeed, the recent search for HCN4-related inheritable arrhythmias has resulted in the finding of four different mutations of the hHcn4 gene, which have been reported to be associated with bradycardia and/or more complex arrhythmic conditions. In neurons, HCN channels display a variety of functions including the regulation of excitability, dendritic integration, plasticity, motor learning, generation of repetitive firing, and others. Defective HCN channels may therefore in principle also contribute to pathological conditions in the nervous system. While full evidence for neuronal HCN channelopathies is not yet available, several indications point to a link between temporal lobe and absence epilepsies and altered distribution of HCN1/HCN2 isoforms. Here we briefly review the current knowledge of HCN-related channelopathies in the heart and the brain.

Keywords

HCN clones Pacemaker SA node Arrhythmia Epilepsy 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Mirko Baruscotti
    • 1
  • Georgia Bottelli
    • 1
  • Raffaella Milanesi
    • 1
  • Jacopo C. DiFrancesco
    • 2
  • Dario DiFrancesco
    • 1
  1. 1.Department of Biomolecular Sciences and Biotechnology, The PaceLabUniversity of Milano and Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata (CIMMBA)MilanoItaly
  2. 2.Department of Neuroscience and Biomedical TechnologiesUniversity of Milano-BicoccaMonzaItaly

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