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This Article Full Text Full Text (PDF) All Versions of this Article: 568/1/155    most recent jphysiol.2005.090951v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saleh, S. Articles by Greenwood, I. Search for Related Content PubMed PubMed Citation Articles by Saleh, S. Articles by Greenwood, I.

Sohag Saleh¹, Shuk Yin M Yeung¹, Sally Prestwich¹, Vladimír Pucovsk¹ and Iain Greenwood¹

¹ Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK

A voltage-gated Na⁺ current was characterised in freshly dissociated mouse portal vein (PV) smooth muscle myocytes. The current was found superimposed upon the relatively slow L-type Ca²⁺ current and was resistant to conventional Ca²⁺ channel blockers but was abolished by external Na⁺ replacement and tetrodotoxin (TTX, 1 µM). The molecular identity of the channel responsible for this conductance was determined by RT-PCR where only the transcripts for Na⁺ channel genes SCN7a, 8a and 9a were detected. The presence of the protein counterparts to the SCN8a and 9a genes (NaV_1.6 and NaV_1.7, respectively) on the individual smooth muscle myocytes were confirmed in immunocytochemistry, which showed diffuse staining around a predominantly plasmalemmal location. TTX inhibited the action potential in individual myocytes generated in the current clamp mode but isometric tissue tension experiments revealed that TTX (1 and 5 µM) had no effect on the inherent mouse PV rhythmicity. However, the Na⁺ channel opener veratridine (10 and 50 µM) significantly increased the length of contraction and the interval between contractions. This effect was not influenced by pre-incubation with atropine, prazosin and propranolol, but was reversed by TTX (1 µM) and completely abolished by nicardipine (1 µM). Furthermore, preincubation with the reverse-mode Na⁺–Ca²⁺ exchange blocker KB-R7943 (10 µM) also inhibited the veratridine response. We have established for the first time the molecular identity of the voltage-gated Na⁺ channel in freshly dispersed smooth muscle cells and have shown that these channels can modulate contractility through a novel mechanism of action possibly involving reverse mode Na⁺–Ca²⁺ exchange.

(Received 19 May 2005; accepted after revision 13 July 2005; first published online 14 July 2005)
Corresponding author I. Greenwood: Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK. Email: i.greenwood{at}sgul.ac.uk

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