Affiliation:
1. From the Center for the Investigation of Membrane Excitability Diseases and Department of Cell Biology and Physiology (C.G.N.), and the Department of Pediatrics (G.K.S., D.K.G.), Washington University School of Medicine, St. Louis, MO.
Abstract
ATP-sensitive potassium (K
ATP
) channels were first discovered in the heart 30 years ago. Reconstitution of K
ATP
channel activity by coexpression of members of the pore-forming inward rectifier gene family (Kir6.1,
KCNJ8
, and Kir6.2
KCNJ11
) with sulfonylurea receptors (SUR1,
ABCC8
, and SUR2,
ABCC9
) of the ABCC protein subfamily has led to the elucidation of many details of channel gating and pore properties. In addition, the essential roles of Kir6.x and SURx subunits in generating cardiac and vascular K
ATP
2
and the detrimental consequences of genetic deletions or mutations in mice have been recognized. However, despite this extensive body of knowledge, there has been a paucity of defined roles of K
ATP
subunits in human cardiovascular diseases, although there are reports of association of a single Kir6.1 variant with the J-wave syndrome in the ECG, and 2 isolated studies have reported association of loss of function mutations in SUR2 with atrial fibrillation and heart failure. Two new studies convincingly demonstrate that mutations in the SUR2 gene are associated with Cantu syndrome, a complex multi-organ disorder characterized by hypertrichosis, craniofacial dysmorphology, osteochondrodysplasia, patent ductus arteriosus, cardiomegaly, pericardial effusion, and lymphoedema. This realization of previously unconsidered consequences provides significant insight into the roles of the K
ATP
channel in the cardiovascular system and suggests novel therapeutic possibilities.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
143 articles.
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