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

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...

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Detalles Bibliográficos
Autores principales: Zhu, Yaohui, Huizinga, Jan D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918088/
https://www.ncbi.nlm.nih.gov/pubmed/18194464
http://dx.doi.org/10.1111/j.1582-4934.2008.00217.x
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author Zhu, Yaohui
Huizinga, Jan D
author_facet Zhu, Yaohui
Huizinga, Jan D
author_sort Zhu, Yaohui
collection PubMed
description 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.
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spelling pubmed-39180882015-04-27 Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel Zhu, Yaohui Huizinga, Jan D J Cell Mol Med Articles 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. Blackwell Publishing Ltd 2008-09 2008-01-11 /pmc/articles/PMC3918088/ /pubmed/18194464 http://dx.doi.org/10.1111/j.1582-4934.2008.00217.x Text en © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Zhu, Yaohui
Huizinga, Jan D
Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel
title Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel
title_full Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel
title_fullStr Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel
title_full_unstemmed Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel
title_short Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel
title_sort nitric oxide decreases the excitability of interstitial cells of cajal through activation of the bk channel
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918088/
https://www.ncbi.nlm.nih.gov/pubmed/18194464
http://dx.doi.org/10.1111/j.1582-4934.2008.00217.x
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