BACKGROUND AND AIM: The action potential plateau of Purkinje fibers is particularly sensitive to tetrodotoxin (TTX) and this could be due to a TXX-sensitive Na(+) current. The expression of TTX-sensitive neuronal Na(V)1.1 and Na(V)1.2 isoforms has been reported in canine Purkinje myocytes. Our aim was to investigate by means of biochemical and functional techniques whether the TTX-sensitive skeletal Na(V)1.4 isoform is also expressed in canine cardiac Purkinje myocytes. METHODS AND RESULTS: Using Na(V)1.4 specific primers, a PCR product corresponding to Na(V)1.4 was amplified from canine Purkinje fibers RNA and confirmed by sequencing and megablast of the gene bank. Confocal indirect immunostaining using anti-Na(V)1.4 antibody demonstrates distinct sarcolemmal staining pattern compared to that of the cardiac isoform Na(V)1.5. Expression of Na(V)1.4 in tsA201 cells yielded a TTX-sensitive Na(+) current with an IC(50) of 10nM. CONCLUSIONS: These results demonstrate the expression of the TTX-sensitive Na(V)1.4 channel in canine cardiac Purkinje myocytes. This novel finding suggests a role of Na(V)1.4 channel in Purkinje myocytes and thus has important clinical implications for the mechanisms and management of ventricular arrhythmias originating in the Purkinje network.
BACKGROUND AND AIM: The action potential plateau of Purkinje fibers is particularly sensitive to tetrodotoxin (TTX) and this could be due to a TXX-sensitive Na(+) current. The expression of TTX-sensitive neuronal Na(V)1.1 and Na(V)1.2 isoforms has been reported in canine Purkinje myocytes. Our aim was to investigate by means of biochemical and functional techniques whether the TTX-sensitive skeletal Na(V)1.4 isoform is also expressed in canine cardiac Purkinje myocytes. METHODS AND RESULTS: Using Na(V)1.4 specific primers, a PCR product corresponding to Na(V)1.4 was amplified from canine Purkinje fibers RNA and confirmed by sequencing and megablast of the gene bank. Confocal indirect immunostaining using anti-Na(V)1.4 antibody demonstrates distinct sarcolemmal staining pattern compared to that of the cardiac isoform Na(V)1.5. Expression of Na(V)1.4 in tsA201 cells yielded a TTX-sensitive Na(+) current with an IC(50) of 10nM. CONCLUSIONS: These results demonstrate the expression of the TTX-sensitive Na(V)1.4 channel in canine cardiac Purkinje myocytes. This novel finding suggests a role of Na(V)1.4 channel in Purkinje myocytes and thus has important clinical implications for the mechanisms and management of ventricular arrhythmias originating in the Purkinje network.
Authors: Volker Haufe; Juan A Camacho; Robert Dumaine; Bernd Günther; Christian Bollensdorff; Gisela Segond von Banchet; Klaus Benndorf; Thomas Zimmer Journal: J Physiol Date: 2005-03-03 Impact factor: 5.182
Authors: Sebastian K G Maier; Ruth E Westenbroek; Kenneth A Schenkman; Eric O Feigl; Todd Scheuer; William A Catterall Journal: Proc Natl Acad Sci U S A Date: 2002-03-12 Impact factor: 11.205
Authors: Manu Ben-Johny; Ivy E Dick; Lingjie Sang; Worawan B Limpitikul; Po Wei Kang; Jacqueline Niu; Rahul Banerjee; Wanjun Yang; Jennifer S Babich; John B Issa; Shin Rong Lee; Ho Namkung; Jiangyu Li; Manning Zhang; Philemon S Yang; Hojjat Bazzazi; Paul J Adams; Rosy Joshi-Mukherjee; Daniel N Yue; David T Yue Journal: Curr Mol Pharmacol Date: 2015 Impact factor: 3.339