Expression of skeletal muscle Na V1.4 Na channel isoform in canine cardiac Purkinje myocytes

Abstract

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 V1.1 and Na V1.2 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 V1.4 isoform is also expressed in canine cardiac Purkinje myocytes. Methods and Results Using Na V1.4 specific primers, a PCR product corresponding to Na V1.4 was amplified from canine Purkinje fibers RNA and confirmed by sequencing and megablast of the gene bank. Confocal indirect immunostaining using anti-Na V1.4 antibody demonstrates distinct sarcolemmal staining pattern compared to that of the cardiac isoform Na V1.5. Expression of Na V1.4 in tsA201 cells yielded a TTX-sensitive Na + current with an IC 50 of 10 nM. Conclusions These results demonstrate the expression of the TTX-sensitive Na V1.4 channel in canine cardiac Purkinje myocytes. This novel finding suggests a role of Na V1.4 channel in Purkinje myocytes and thus has important clinical implications for the mechanisms and management of ventricular arrhythmias originating in the Purkinje network.