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


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.
Qu
Yongxia
Y
VA New York Harbor Healthcare System, Brooklyn, NY 11209, USA.
Karnabi
Eddy
E
Chahine
Mohamed
M
Vassalle
Mario
M
Boutjdir
Mohamed
M
D000200:Action Potentials; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004285:Dogs; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D032342:Muscle Cells / Q000502:physiology*; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics*; D018482:Muscle, Skeletal / Q000502:physiology*; D011690:Purkinje Fibers / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection
D017931:DNA Primers; D009124:Muscle Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015222:Sodium Channels; D013779:Tetrodotoxin