title: Expression of skeletal muscle Na(V)1.4 Na channel isoform in canine cardiac Purkinje myocytes.
abstract: 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.
authors.affiliation: VA New York Harbor Healthcare System, Brooklyn, NY 11209, USA.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Qu
authors.forename: Eddy
authors.initials: E
authors.lastname: Karnabi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chahine
authors.forename: Mario
authors.initials: M
authors.lastname: Vassalle
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boutjdir
mesh_terms: 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
chemical_list: D017931:DNA Primers; D009124:Muscle Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015222:Sodium Channels; D013779:Tetrodotoxin