Expression of skeletal muscle Na(V)1.4 Na channel isoform in canine cardiac Purkinje myocytes.

Abstract:

<p><b>BACKGROUND AND AIM: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>