Referenced in: none

Automatically associated channels: Kir2.3 , Nav1.5

Title: A Novel Disease Gene for Brugada Syndrome: Sarcolemmal Membrane-Associated Protein Gene Mutations Impair Intracellular Trafficking of hNav1.5.

Authors: Taisuke Ishikawa, Akinori Sato, Cherisse A Marcou, David J Tester, Michael J Ackerman, Lia Crotti, Peter J Schwartz, Young Keun On, Jeong-Euy Park, Kazufumi Nakamura, Masayasu Hiraoka, Kiyoshi Nakazawa, Harumizu Sakurada, Takuro Arimura, Naomasa Makita, Akinori Kimura

Journal, date & volume: Circ Arrhythm Electrophysiol, 2012 Dec 1 , 5, 1098-107

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23064965

Abstract
Mutations in genes including SCN5A encoding the α-subunit of the cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function of cardiac ion channels, but more than two-thirds of Brugada syndrome remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential in excitation of cardiomyocytes, and sarcolemmal membrane-associated protein (SLMAP) is a protein of unknown function localizing at T-tubules and sarcoplasmic reticulum.We analyzed 190 unrelated Brugada syndrome patients for mutations in SLMAP. Two missense mutations, Val269Ile and Glu710Ala, were found in heterozygous state in 2 patients but were not found in healthy individuals. Membrane surface expression of hNav1.5 in the transfected cells was affected by the mutations, and silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5. Whole-cell patch-clamp recordings of hNav1.5-expressing cells transfected with mutant SLMAP confirmed the reduced hNav1.5 current.The mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel.