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Serotonin stimulates endothelial release of nitric oxide causing hyperpolarization by activation of ATP‐sensitive K‐channels in guinea pig inner ear artery
Author(s) -
Yang YuQin,
Nuttall Alfred L,
Jiang ZhiGen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a283-b
Subject(s) - hyperpolarization (physics) , apamin , membrane potential , serotonin , medicine , channel blocker , endocrinology , chemistry , nitric oxide , charybdotoxin , depolarization , potassium channel , pharmacology , biophysics , receptor , biology , calcium , nuclear magnetic resonance spectroscopy , organic chemistry
Serotonin (5‐HT) is a widely distributed neurotransmitter and a local hormone, thus plays multiple pivotal functions in mammals, including a role in systemic and local circulation control. Serotonin is also implicated in the pathophysiology of tinnitus and Meniere’s disease. Using intracellular recording techniques, we investigated cellular actions and pharmacology of 5‐HT in the in vitro spiral modiolar artery (SMA) and found: 1) 5‐HT (1–30 μM) and agonists for 5‐HT receptor subtypes 5‐CT and (+)‐8‐OH‐DPAT all concentration‐dependently caused a hyperpolarization in the majority of cells that had a low resting potential (RP, ~−40 mV) but essentially no effect in high RP (~−75 mV) cells. 2) 5‐HT‐induced hyperpolarization was completely blocked by 10 μM clozapine or 1 μM spiperone, which sometimes unmasked a depolarization (2–4 mV). The latter was sensitive to 1 μM ritanserin. 3) 5‐HT‐hyperpolarization was suppressed by 100 μM N G ‐Nitro‐L‐arginine‐methyl ester (L‐NAME), a nitric oxide (NO) synthase inhibitor,and 3 μM glipizide, a ATP‐sensitive potassium channel (K ATP ) blocker,but not affected by 100 μM Ba 2+ . 4) 5‐HT‐hyperpolarization in smooth muscle (SMC) but not that in endothelial cells (EC) was suppressed by 18β‐glycyrrhetinic acid (30 μM, a gap junction blocker). We conclude that serotonin mainly acts on 5‐HT 1 or alike receptors in the EC membrane to cause a release of NO, the latter in turn induces an opening of the K ATP and thus a membrane hyperpolarization in endothelial cells. The hyperpolarization spreads to smooth muscle cells via gap junction electric coupling. Supported by NIH NIDCD DC 004716 (ZGJ) and DC00141 (ALN).