TRPM4 channels in the cardiovascular system.
The non-selective Transient Receptor Potential Melastatin 4 (TRPM4) cation channel is abundantly expressed in cardiac cells, being involved in several aspects of cardiac rhythmicity, including cardiac conduction, pace making and action-potential repolarization. Dominantly inherited mutations in the TRPM4 gene are associated with the cardiac bundle-branch disorder progressive familial heart block type I (PFHBI) and isolated cardiac conduction disease (ICCD) giving rise to atrio-ventricular conduction block (AVB), right bundle branch block, bradycardia, and the Brugada syndrome. The mutant phenotypes closely resemble those associated with mutations in the SCN5A gene, encoding the voltage-gated Na(+) channel NaV1.5. These observations and the unexpected partnership with sulfonylurea-receptors (SURs) makes the TRPM4 channel a promising novel target for treatment of cardiac disorders.
Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA.
Martin
M
Kruse
Institute of Physiology, Universitätsklinikum des Saarlandes, Homburg, Germany. Electronic address: oupon@t-online.de.
Olaf
O
Pongs
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000378:metabolism; D006801:Humans; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D050053:TRPM Cation Channels