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1.  New Insights in the Contribution of Voltage-Gated Nav Channels to Rat Aorta Contraction 
PLoS ONE  2009;4(10):e7360.
Background
Despite increasing evidence for the presence of voltage-gated Na+ channels (Nav) isoforms and measurements of Nav channel currents with the patch-clamp technique in arterial myocytes, no information is available to date as to whether or not Nav channels play a functional role in arteries. The aim of the present work was to look for a physiological role of Nav channels in the control of rat aortic contraction.
Methodology/Principal Findings
Nav channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Nav channels and smooth muscle α-actin using specific antibodies. In parallel, using real time RT-PCR, we identified three Nav transcripts: Nav1.2, Nav1.3, and Nav1.5. Only the Nav1.2 isoform was found in the intact media and in freshly isolated myocytes excluding contamination by other cell types. Using the specific Nav 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 Nav 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 µM) and blocked by TTX (1 µM). KB-R7943, an inhibitor of the reverse mode of the Na+/Ca2+ exchanger, mimicked the effect of TTX and had no additive effect in presence of TTX.
Conclusions/Significance
These results define a new role for Nav channels in arterial physiology, and suggest that the TTX-sensitive Nav1.2 isoform, together with the Na+/Ca2+ exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization.
doi:10.1371/journal.pone.0007360
PMCID: PMC2752992  PMID: 19809503
2.  Consequences of reduced production of NO on vascular reactivity of porcine coronary arteries after angioplasty: importance of EDHF 
British Journal of Pharmacology  2002;136(8):1153-1161.
The consequences of the reduced production of nitric oxide (NO) by cells from regenerated endothelium were investigated by measuring membrane potential of smooth muscle cells (SMCs), isometric tension and cyclic nucleotides content in porcine coronary arteries with intimal thickening, four weeks following angioplasty.Under basal conditions, SMCs of coronary arteries with regenerated endothelium were depolarized by 10 mV. This depolarization was associated with 82% decreased level of cGMP without alteration in cAMP.Sodium nitroprusside (SNP, 1 μM) repolarized SMCs of the previously denuded coronary arteries. This repolarization was abolished by 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and not suppressed by glibenclamide (10 μM), iberiotoxin (IbTX, 100 nM) and the combination of charybdotoxin (ChTX, 40 nM) plus apamin (100 nM).Four-aminopyridine (4-AP, 1-5 mM) generated spontaneous rhythmic activities only in coronary arteries with regenerated endothelium which were abolished by SNP. Nevertheless, 4-AP did not suppress the repolarization induced by SNP.In vascular segments with regenerated endothelium, contracted with prostaglandin F2α (PGF2α), relaxation to bradykinin (BK, 30 nM) was unaltered despite a reduced production of cGMP (−70%). Indomethacin (10 μM) plus Nω-nitro-L-arginine (L-NA, 30 μM) reduced relaxation (−12% and −35% for native and regenerated endothelium, respectively) but did not abolish it.The hyperpolarizations induced by BK were not altered by the presence of indomethacin and L-NA and were unchanged in segments with regenerated endothelium.These data are consistent with a contribution of impairment in NO production to the depolarization of SMCs. Nevertheless, EDHF responses to BK are sufficient to maintain a normal relaxation after angioplasty.
doi:10.1038/sj.bjp.0704828
PMCID: PMC1573455  PMID: 12163348
Regenerated endothelium; endothelium-derived hyperpolarizing factor; nitric oxide; cyclic nucleotides; bradykinin
3.  Potassium ions and endothelium-derived hyperpolarizing factor in guinea-pig carotid and porcine coronary arteries 
British Journal of Pharmacology  1999;127(1):27-34.
Experiments were designed to determine in two arteries (the guinea-pig carotid and the porcine coronary arteries) whether or not the endothelium-derived hyperpolarizing factor (EDHF) can be identified as potassium ions, and to determine whether or not the inwardly rectifying potassium current and the Na+/K+ pump are involved in the hyperpolarization mediated by EDHF.The membrane potential of vascular smooth muscle cells was recorded with intracellular microelectrodes in the presence of Nω-L-nitro-arginine (L-NA) and indomethacin.In vascular smooth muscle cells of guinea-pig carotid and porcine coronary arteries, acetylcholine and bradykinin induced endothelium-dependent hyperpolarizations (−18±1 mV, n=39 and −19±1 mV, n=7, respectively). The hyperpolarizations were not affected significantly by ouabain (1 μM), barium chloride (up to 100 μM) or the combination of ouabain plus barium.In both arteries, increasing extracellular potassium concentration by 5 or 10 mM induced either depolarization or in a very few cases small hyperpolarizations which never exceeded 2 mV.In isolated smooth muscle cells of the guinea-pig carotid artery, patch-clamp experiments shows that only 20% of the vascular smooth muscle cells expressed inwardly rectifying potassium channels. The current density recorded was low (0.5±0.1 pA pF−1, n=8).These results indicate that, in two different vascular preparations, barium sensitive-inwardly rectifying potassium conductance and the ouabain sensitive-Na+/K+ pump are not involved in the EDHF-mediated hyperpolarization. Furthermore, potassium did not mimic the effect of EDHF pointing out that potassium and EDHF are not the same entity in those arteries.
doi:10.1038/sj.bjp.0702493
PMCID: PMC1565980  PMID: 10369452
Potassium; endothelium-derived hyperpolarizing factor; EDHF; endothelium; vascular smooth muscle cells; inwardly rectifying potassium current; Na+/K+ pump; ouabain; barium

Results 1-3 (3)