New Insights in the Contribution of Voltage-Gated Nav Channels to Rat Aorta Contraction
2009
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 a-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 255.961.4 mV to 245.961.2 mV at 10 mmol/L as measured with microelectrodes), triggered a contraction potentiated by veratridine (100 mM) and blocked by TTX (1 mM). 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/Significance: These results define a new role for Nav channels in arterial physiology, and suggest that the TTXsensitive Nav1.2 isoform, together with the Na + /Ca 2+ exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
41
References
13
Citations
NaN
KQI