Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery

Zhi Gen Jiang, Alfred L. Nuttall, Hui Zhao, Chun Fu Dai, Bing Cai Guan, Jun Qiang Si, Yu Qin Yang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro cochlear spiral modiolar artery (SMA) was investigated by intracellular recording combined with dye labelling of recorded cells and immunocytochemistry. We found the following. (1) The ACh-hyperpolarization was prominent only in cells that had a low resting potential (less negative than -60mV). ACh-hyperpolarization was reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by Nω-nitro-L-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid. (2) Ba2+ (100 μm) and ouabain (I μm) each attenuated ACh-hyperpolarization by ∼30% in smooth muscle cells (SMCs) but had only slight or no inhibition in endothelial cells (ECs). A combination of Ba2+ and 18β-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in SMCs. (3) High K+ (10 mM) induced a smaller hyperpolarization in ECs than in SMCs, with an amplitude ratio of 0.49: 1. Ba2+ blocked the K+-induced hyperpolarization by ∼85% in both cell types, whereas ouabain inhibited K+ -hyperpolarization differently in SMCs (19%) and ECs (35%) and increased input resistance. 18β-Glycyrrhetinic acid blocked the high K+ -hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected by confocal microscopy in cells recorded with a propidium iodide-containing electrode for longer than 30 min. A sparse plexus of choline acetyltransferase-immunoreactive (ChAT) fibres was observed around the SMA and its up-stream arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked by 4-DAMP in half of the cells tested. We conclude that ACh-induced hyperpolarization originates from ECs via activation of Ca2+ -activated potassium channels, and is independent of the release of NO, cyclo-oxygenase or cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells involves two mechanisms: (a) electrical spread of the hyperpolarization from the endothelium, and (b) activation of inward rectifier K+ channels (Kir) and Na+ -K+ pump current by elevated interstitial K+ released from the endothelial cells, these being responsible for about 60% and 40% of the hyperpolarization, respectively. The role ratio of Kir and pump current activation is at 8: 1 or less.

Original languageEnglish (US)
Pages (from-to)475-487
Number of pages13
JournalJournal of Physiology
Issue number2
StatePublished - Apr 15 2005

ASJC Scopus subject areas

  • Physiology


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