Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel

Yaohui Zhu, Jan D. Huizinga

Research output: Contribution to journalArticle

Abstract

Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from -80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at -25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability.

Original languageEnglish (US)
Pages (from-to)1718-1727
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume12
Issue number5A
DOIs
StatePublished - Sep 2008
Externally publishedYes

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Interstitial Cells of Cajal
Large-Conductance Calcium-Activated Potassium Channels
Nitric Oxide
Nystatin
Nitroprusside
Noise
Nitrergic Neurons
Calcium
Myenteric Plexus
Nitroarginine
Cobalt
Nerve Fibers
Ganglia
Small Intestine
Immunohistochemistry
Communication
Antibodies
iberiotoxin

Keywords

  • Calcium
  • Pacemaker cells
  • Slow wave

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel. / Zhu, Yaohui; Huizinga, Jan D.

In: Journal of Cellular and Molecular Medicine, Vol. 12, No. 5A, 09.2008, p. 1718-1727.

Research output: Contribution to journalArticle

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