Release and elementary mechanisms of nitric oxide in hair cells

Ping Lv, Adrian Rodriguez-Contreras, Hyo Jeong Kim, Jun Zhu, Dongguang Wei, Sihn Choong-Ryoul, Emily Eastwood, Karen Mu, Snezana Levic, Haitao Song, Petrov Y. Yevgeniy, Peter J S Smith, Ebenezer N. Yamoah

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The enzyme nitric oxide (NO) synthase, that produces the signaling molecule NO, has been identified in several cell types in the inner ear. However, it is unclear whether a measurable quantity of NO is released in the inner ear to confer specific functions. Indeed, the functional significance of NO and the elementary cellular mechanism thereof are most uncertain. Here, we demonstrate that the sensory epithelia of the frog saccule release NO and explore its release mechanisms by using self-referencing NO-selective electrodes. Additionally, we investigated the functional effects of NO on electrical properties of hair cells and determined their underlying cellular mechanism. We show detectable amounts of NO are released by hair cells (>50 nM). Furthermore, a hair-cell efferent modulator acetylcholine produces at least a threefold increase in NO release. NO not only attenuated the baseline membrane oscillations but it also increased the magnitude of current required to generate the characteristic membrane potential oscillations. This resulted in a rightward shift in the frequency- current relationship and altered the excitability of hair cells. Our data suggest that these effects ensue because NO reduces whole cell Ca2+ current and drastically decreases the open probability of single-channel events of the L-type and non L-type Ca 2+ channels in hair cells, an effect that is mediated through direct nitrosylation of the channel and activation of protein kinase G. Finally, NO increases the magnitude of Ca2+-activated K+ currents via direct NO nitrosylation. We conclude that NO-mediated inhibition serves as a component of efferent nerve modulation of hair cells.

Original languageEnglish (US)
Pages (from-to)2494-2505
Number of pages12
JournalJournal of Neurophysiology
Volume103
Issue number5
DOIs
StatePublished - May 2010

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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    Lv, P., Rodriguez-Contreras, A., Kim, H. J., Zhu, J., Wei, D., Choong-Ryoul, S., Eastwood, E., Mu, K., Levic, S., Song, H., Yevgeniy, P. Y., Smith, P. J. S., & Yamoah, E. N. (2010). Release and elementary mechanisms of nitric oxide in hair cells. Journal of Neurophysiology, 103(5), 2494-2505. https://doi.org/10.1152/jn.00017.2010