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Accueil > Bibliographie > Activation of neurokinin 3 receptor increases Nav1.9 current in enteric (...)

Activation of neurokinin 3 receptor increases Nav1.9 (...)

J Physiol. 2009 Apr ;587(Pt 7):1461-79
Activation of neurokinin 3 receptor increases Nav1.9 current in enteric neurons.
Copel C, Osorio N, Crest M, Gola M, Delmas P, Clerc N.

The primary afferent neurons (IPANs) of the guinea pig enteric nervous system express Nav1.9 sodium channels that produce a persistent TTX-resistant current having a low activation threshold and slow gating kinetics. These neurons receive slow EPSPs induced mainly by the activation of neurokinin 3 receptors (NK3r). Here, we demonstrate that senktide, a specific NK3r agonist, potentiates the Nav1.9 current (INav1.9) in IPANs. Using whole-cell patch-clamp recordings from IPANs in duodenum longitudinal muscle/myenteric plexus preparations, we show that short (1 to 5 s) and long (up to 1 min) applications of senktide, increase the INav1.9 peak current up to 13 fold. The effect, blocked by a NK3r antagonist, SB235375 is transient, lasting 2 minutes and is due to a negative shift of the activation voltage by 20 mV and of fast inactivation by 10 mV. As a consequence, the window current resulting from the product of the activation and fast inactivation curves is shifted and enlarged. The transient effect of senktide is likely to be due to the fast desensitisation of NK3r. PKC activation with phorbol or oleoyl acetylglycerol also increases INav1.9, although persistently, by inducing similar voltage dependent changes. Current clamp experiments showed that INav1.9 modulation by senktide lowers action potential threshold and increases excitability. The increase in INav1.9 by NK3r activation is also likely to amplify slow EPSPs generated in the IPANs. These changes in excitability potentially have a profound effect of the entire enteric synaptic circuit and ultimately on gut motility and secretion.

PubMed

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