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http://dx.doi.org/10.14348/molcells.2014.0167

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons  

Kim, Young-Hwan (Department of Physiology, Yonsei University College of Medicine)
Ahn, Duck-Sun (Department of Physiology, Yonsei University College of Medicine)
Kim, Myeong Ok (Department of Biology and Applied Life Science (BK21 Plus), College of Natural Sciences, Gyeongsang National University)
Joeng, Ji-Hyun (Department of Physiology, Yonsei University College of Medicine)
Chung, Seungsoo (Department of Physiology, Yonsei University College of Medicine)
Publication Information
Molecules and Cells / v.37, no.11, 2014 , pp. 804-811 More about this Journal
Abstract
The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type $Ca^{2+}$ currents ($I_{Ca-N}$) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated $Ca^{2+}$ currents ($I_{Ca}$), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on $I_{Ca}$. This PAR-2-induced inhibition was almost completely prevented by ${\omega}$-CgTx, a potent N-type $Ca^{2+}$ channel blocker, suggesting the involvement of N-type $Ca^{2+}$ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited $I_{Ca-N}$ in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ${\omega}$-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type $Ca^{2+}$ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type $Ca^{2+}$ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals.
Keywords
celiac ganglion; hypotension; N-type $Ca^{2+}$ channel; peripheral sympathetic output; protease-activated receptor 2;
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