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Increased sensitivity of serotonin on the voltage-dependent K+ channels in mesenteric arterial smooth muscle cells of OLETF rats

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Author(s)
Dae Kyu SongYung E. EarmJin HanEun A. KoWon Sun ParkAmy L. FirthDa Hae HongSeong Woo ChoiHye-Jin HeoMin Hee KimJung Hyun NohJae-Hong KoNari Kim
Keimyung Author(s)
Song, Dae Kyu
Department
Dept. of Physiology (생리학)
Journal Title
Progress in Biophysics and Molecular Biology
Issued Date
2010
Volume
103
Issue
1
Keyword
DiabetesSerotonin (5-HT)Voltage-dependent Kþ channelsOtsuka Long-Evans Tokushima fatty (OLETF)Mesenteric arterial smooth muscle cells
Abstract
This study examined the mechanisms of hypertension in diabetes. We investigated the effects of serotonin (5-HT) on voltage-dependent K+ (Kv) channel activity, vasoconstriction, 5-HT receptor expression levels, and the involvement of protein kinase C (PKC) in mesenteric arteries of Otsuka Long-Evans Tokushima fatty (OLETF) rats compared with Long-Evans Tokushima Otsuka (LETO) rats. Blood pressure, body weight, blood glucose level, and mesenteric arterial wall thickness were greater in OLETF rats. The 5-HT-induced vasoconstriction of mesenteric arteries was greater in OLETF rats than in LETO rats and inhibited by the 5-HT2A inhibitor inhibitor, ketanserin. The Kv currents in mesenteric arterial smooth muscle cells (MASMCs), determined using a perforated patch clamp technique, was inhibited by 1 mM 4-AP (42.5 ± 4.1% vs. 63.5 ± 2.3% in LETO vs. OLETF rats at +40 mV), but was insensitive to 1 mM TEA and 100 nM iberiotoxin. The inhibition of Kv current by 1 μM 5-HT in MASMCs was greater in OLETF rats than in LETO rats (17.1 ± 2.2% vs. 33.2 ± 2.7% in LETO vs. OLETF rats at +40 mV), and the inhibition was prevented by treatment with the PKCα- and β- selective inhibitor, Gö6976. The expression level of 5-HT2A, but not 5-HT2B, receptor and the expression levels of total PKC, PKCβ, and PKCε, but not PKCα, were higher in the mesenteric arteries of OLETF rats compared with LETO rats. The enhanced expression of 5-HT2A receptor together with PKCβ may promote mesenteric vasoconstriction and increase vascular resistance in OLETF rats.

Keywords
Diabetes;
Serotonin (5-HT);
Voltage-dependent K+ channels;
Otsuka Long-Evans Tokushima fatty (OLETF);
Mesenteric arterial smooth muscle cells
Keimyung Author(s)(Kor)
송대규
Publisher
School of Medicine
Citation
Dae Kyu Song et al. (2010). Increased sensitivity of serotonin on the voltage-dependent K+ channels in mesenteric arterial smooth muscle cells of OLETF rats. Progress in Biophysics and Molecular Biology, 103(1), 88–94. doi: 10.1016/j.pbiomolbio.2010.02.003
Type
Article
ISSN
0079-6107
Source
https://www.sciencedirect.com/science/article/pii/S0079610710000258?via%3Dihub
DOI
10.1016/j.pbiomolbio.2010.02.003
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33452
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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