title: New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction.
abstract: BACKGROUND
  Despite increasing evidence for the presence of voltage-gated Na(+) channels (Na(v)) isoforms and measurements of Na(v) channel currents with the patch-clamp technique in arterial myocytes, no information is available to date as to whether or not Na(v) channels play a functional role in arteries. The aim of the present work was to look for a physiological role of Na(v) channels in the control of rat aortic contraction.
  
  
  RESULTS
  Na(v) channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Na(v) channels and smooth muscle alpha-actin using specific antibodies. In parallel, using real time RT-PCR, we identified three Na(v) transcripts: Na(v)1.2, Na(v)1.3, and Na(v)1.5. Only the Na(v)1.2 isoform was found in the intact media and in freshly isolated myocytes excluding contamination by other cell types. Using the specific Na(v) channel agonist veratridine and antagonist tetrodotoxin (TTX), we unmasked a contribution of these channels in the response to the depolarizing agent KCl on rat aortic isometric tension recorded from endothelium-denuded aortic rings. Experimental conditions excluded a contribution of Na(v) channels from the perivascular sympathetic nerve terminals. Addition of low concentrations of KCl (2-10 mM), which induced moderate membrane depolarization (e.g., from -55.9+/-1.4 mV to -45.9+/-1.2 mV at 10 mmol/L as measured with microelectrodes), triggered a contraction potentiated by veratridine (100 microM) and blocked by TTX (1 microM). KB-R7943, an inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger, mimicked the effect of TTX and had no additive effect in presence of TTX.
  
  
  CONCLUSIONS
  These results define a new role for Na(v) channels in arterial physiology, and suggest that the TTX-sensitive Na(v)1.2 isoform, together with the Na(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization.
authors.affiliation: INSERM U637, Université Montpellier 1 & 2, Montpellier, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Fort
authors.forename: Magali
authors.initials: M
authors.lastname: Cordaillat
authors.forename: Catherine
authors.initials: C
authors.lastname: Thollon
authors.forename: Guillermo
authors.initials: G
authors.lastname: Salazar
authors.forename: Ilana
authors.initials: I
authors.lastname: Mechaly
authors.forename: Nicole
authors.initials: N
authors.lastname: Villeneuve
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vilaine
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
authors.forename: Anne
authors.initials: A
authors.lastname: Virsolvy
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D008297:Male; D008564:Membrane Potentials; D032342:Muscle Cells / Q000473:pathology; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009711:Nucleotides / Q000737:chemistry; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000737:chemistry* / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000737:chemistry; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009711:Nucleotides; D020033:Protein Isoforms; C568253:Scn2A protein, rat; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D013890:Thiourea