New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction.
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2752992?pdf=render |
| _version_ | 1818989443884777472 |
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| author | Aurélie Fort Magali Cordaillat Catherine Thollon Guillermo Salazar Ilana Mechaly Nicole Villeneuve Jean-Paul Vilaine Sylvain Richard Anne Virsolvy |
| author_facet | Aurélie Fort Magali Cordaillat Catherine Thollon Guillermo Salazar Ilana Mechaly Nicole Villeneuve Jean-Paul Vilaine Sylvain Richard Anne Virsolvy |
| author_sort | Aurélie Fort |
| collection | DOAJ |
| description | 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 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/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(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization. |
| first_indexed | 2024-12-20T19:38:34Z |
| format | Article |
| id | doaj.art-91d0449526af42ba8e050217b751b7af |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T19:38:34Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-91d0449526af42ba8e050217b751b7af2022-12-21T19:28:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-01410e736010.1371/journal.pone.0007360New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction.Aurélie FortMagali CordaillatCatherine ThollonGuillermo SalazarIlana MechalyNicole VilleneuveJean-Paul VilaineSylvain RichardAnne VirsolvyBACKGROUND: 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 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/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(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization.http://europepmc.org/articles/PMC2752992?pdf=render |
| spellingShingle | Aurélie Fort Magali Cordaillat Catherine Thollon Guillermo Salazar Ilana Mechaly Nicole Villeneuve Jean-Paul Vilaine Sylvain Richard Anne Virsolvy New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. PLoS ONE |
| title | New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. |
| title_full | New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. |
| title_fullStr | New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. |
| title_full_unstemmed | New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. |
| title_short | New insights in the contribution of voltage-gated Na(v) channels to rat aorta contraction. |
| title_sort | new insights in the contribution of voltage gated na v channels to rat aorta contraction |
| url | http://europepmc.org/articles/PMC2752992?pdf=render |
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