Mutations in the SCN5A gene encoding the cardiac sodium channel are linked to primary electrical diseases including long QT syndrome, Brugada syndrome, and cardiac conduction defects.
Time for primary review 32 days. The voltage-gated cardiac sodium channel is responsible for the generation of the rapid upstroke of the myocardial action potential and thereby plays a central role in excitability of myocardial cells. In addition, since the action potential upstroke velocity — in conjunction with the extent of intercellular communication via gap junctions 1 — also determines impulse conduction velocity in cardiac tissue, this channel also plays a vital role in impulse propagation. Mutations in the gene encoding this channel (SCN 5 A ; Section 2. 1) have been linked to three forms of primary electrical disease — the long QT syndrome (LQTS) 2, the Brugada syndrome (BS) 3 and cardiac conduction defects 4. The elucidation of the pathophysiological mechanisms of these mutant Na+ channels would ultimately enable more specific pharmacological intervention in the management of these syndromes and other related arrhythmias. The cardiac Na+ channel (see Ref. 5 for review) is a member of the voltage-dependent family of Na+ channels (see Ref. 6 for review). These channels consist of heteromeric assemblies of an α-subunit, the pore-forming component, the function of which is modulated by association with one or two ancillary β-subunits. ### 2. 1 α-Subunit The human cardiac Na+ channel α-subunit is a heavily glycosylated protein of ∼260 kDa consisting of 2016 amino acid residues 7. It is encoded by the SCN 5 A gene 8, which is located on chromosome 3p21 9. At least 11 other different genes that encode highly homologous sodium channel α-subunit isoforms expressed in the heart, muscle and nervous system have been hitherto identified in man (http: //www. ncbi. nlm. nih. gov/entrez/query. fcgi? db=Nucleotide). They display a modular architecture (Fig. 1), which consists of four internally homologous domains (DI–DIV) each made up of six transmembrane segments (S1–S6). The interdomain linkers and the N- and … * Corresponding author. Tel.: +31-20-566-3265; fax: +31-20-697-5458 a. a. wildeatamc. uva. nl
Connie R. Bezzina (Thu,) conducted a review in Inherited arrhythmia syndromes (long QT syndrome, Brugada syndrome, cardiac conduction defects). Mutations in the SCN5A gene encoding the cardiac sodium channel are linked to primary electrical diseases including long QT syndrome, Brugada syndrome, and cardiac conduction defects.
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