Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig in vitro spiral modiolar artery

Zhi-Gen Jiang, Xiao Shi, Hui Zhao, Jun Qiang Si, Alfred Nuttall

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Nitric oxide (NO) is a potent vasodilating agent implicated in cochlear blood flow regulation. We recently demonstrated that exogenously applied NO donor DPTA-NONOate hyperpolarizes both endothelial and smooth muscle cells of in vitro spiral modiolar artery (SMA) via activation of ATP-sensitive K + channels (KATP). Also, NO was detected in the SMA cells by NO indicator dye in the in vitro basal condition. Using intracellular recording techniques, electrochemical NO-sensing measurement, and a vaso-diameter video tracking method, we investigated the basal release of NO from the in vitro SMA and its role in the vascular function. We found that (1) 300 μM L-NAME, a NO synthase inhibitor, and 3 μM glipizide caused a depolarization of ∼4.5 and ∼3.2 mV, respectively, in cells with a resting potential less negative than -60 mV; (2) NO sensor in the close vicinity of the SMA detected a NO concentration of ∼50 nM that was suppressed by L-NAME and enhanced by L-arginine (1-1000 μM); (3) NO donor DPTA-NONOate (0.1-30 μM) applications produced about 8-245 nM of NO in the recording bath. These data indicate a NO concentration-hyperpolarization relation, with an EC50 of 22 nM. (4) Finally, L-NAME but not glipizide produced a 4.8% reduction in SMA diameter (∼50 μm) in the majority of SMAs, whereas NONOate (10 μM) always caused a dilation. Both the induced constriction and dilation were not significantly affected by 3 μM glipizide. We conclude that a significant amount of NO (>50 nM) is tonically released from the in vitro SMA, which is above the EC50 for activation of KATP, and thus contributes to the membrane polarization. The basal release of NO also contributes to vasotone relaxation, but the KATP activation appears to play little role in the relaxation of the in vitro SMA.

Original languageEnglish (US)
Pages (from-to)92-100
Number of pages9
JournalHearing Research
Volume189
Issue number1-2
DOIs
Publication statusPublished - Mar 2004

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Keywords

  • Arteriole
  • Cochlea
  • Nitric oxide synthase
  • NO release
  • Potassium channel

ASJC Scopus subject areas

  • Sensory Systems

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