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

• Published in: Molecules and cells Vol. 37; no. 11; pp. 804 - 811
• Main Authors: Kim, Young-Hwan, Ahn, Duck-Sun, Kim, Myeong Ok, Joeng, Ji-Hyun, Chung, Seungsoo
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.11.2014; 한국분자세포생물학회
• Subjects: Action Potentials - drug effects; Animals; Calcium Channels, N-Type - metabolism; Ganglia, Sympathetic - enzymology; Hypotension - metabolism; Male; Mesenteric Arteries - physiology; Neurons - metabolism; Oligopeptides - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, PAR-2 - agonists; Receptor, PAR-2 - metabolism; 생물학; hypotension; peripheral sympathetic output; protease-activated receptor 2; celiac ganglion; N-type Ca2+ channel
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2014.0167

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 ω-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 ω-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.