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KMID : 0811720070110000085
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 0 p.85 ~ p.0
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5-HT-induced Inhibition of KV Channels via 5-HT2A Receptor Contributes to Mesenteric Artery Constriction in Rat
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Kim Jae-Gon
Sung Dong-Jun
Noh Hyun-Ju
Bae Young-Min
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Abstract
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In this study, using the nystatin-perforated patch configuration of the patch-clamp technique and isometric tension measurement of artery rings, we examined the hypothesis that inhibition of KV current via 5-HT2A receptor plays a role in 5-HT-induced vasoconstriction in rat mesenteric artery.
Nifedipine (1μM), a selective and potent L-type Ca2+ channel inhibitor, largely suppressed the 5-HT-induced mesenteric vasoconstriction, indicating that the 5-HT-induced vasoconstriction is largely contributed by Em depolarization. 4-aminopyridine (4-AP, 10 mM), a relatively selective KV channel blocker in arterial smooth muscle, caused marked mesenteric artery constrictions, whereas tetraethylammonium (TEA, 1 mM) had no effect. These results support the hypothesis that 5-HT- induced inhibition of KV channels and subsequent Em depolarization contribute to mesenteric artery constriction. Next, we examined whether 5-HT-induced inhibition of KV channels is mediated via 5-HT2A receptor. Under control condition, 5-HT induced about 40% inhibition of the KV current independent of membrane potential. A 5-HT2 receptor agonist α-methyl 5-HT induced similar inhibitory effects on the KV currents. However, neither anpirtoline, a 5-HT1B receptor subtype agonist, nor BW-723C86, a 5-HT2B receptor agonist, induced inhibition of KV current. In addition, pretreatment of ketanserin, a selective 5-HT2A receptor antagonist completely suppressed 5-HT-induced KV current inhibition. The contractile responses of mesenteric arterial rings to above 5-HT receptor subtype agonist and antagonist were completely corresponded with the KV channel response. These results suggest that 5-HT-induced inhibition of KV current is mediated via 5-HT2A receptor and this KV inhibition plays the major role in 5-HT-induced vasoconstriction in rat mesenteric artery.
Source: Korean Journal of Physiology & Pharmacology.2007 Oct;11(Suppl II):S81-S81
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KEYWORD
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5-HT, Kv channel, Mesenteric artery
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