New Insights In The Contribution Of Voltage-Gated Na-V Channels To Rat Aorta Contraction
PLOS ONE(2009)
摘要
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.Methodology/Principal Findings: Na-v channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Na-v channels and smooth muscle a-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 mu M) and blocked by TTX (1 mu M). 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 Na-v channels in arterial physiology, and suggest that the TTX-sensitive Na(v)1.2 isoform, together with the Na+/Ca2+ exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization.
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关键词
patch clamp technique,electrophysiology,engineering,muscle cells,nucleotides,sodium channels,membrane potentials,physics,medicine,chemistry,biology
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