論文

査読有り
2007年12月

Nitric oxide activates leak K+ currents in the presumed cholinergic neuron of basal Forebrain

JOURNAL OF NEUROPHYSIOLOGY
  • Youngnam Kang
  • ,
  • Yoshie Dempo
  • ,
  • Atsuko Ohashi
  • ,
  • Mitsuru Saito
  • ,
  • Hiroki Toyoda
  • ,
  • Hajime Sato
  • ,
  • Hisashi Koshino
  • ,
  • Yoshinobu Maeda
  • ,
  • Toshihiro Hirai

98
6
開始ページ
3397
終了ページ
3410
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1152/jn.00536.2007
出版者・発行元
AMER PHYSIOLOGICAL SOC

Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K+ channels. Many neuro-modulators closing leak K+ channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K+ channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromo-guanosine-3', 5' -cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at -70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K+ equilibrium potential (E-K) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K+ current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 mu M Rp-8-bromo-beta-phenyl-1, N-2-ethenoguanosine 3',5' -cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than E K and close to the reversal potential of Na+ -K+ pump current. These observations strongly suggest that NO activates leak K+ channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na+ -K+ pump through ATP depletion.

Web of Science ® 被引用回数 : 25

リンク情報
DOI
https://doi.org/10.1152/jn.00536.2007
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17928563
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000251775700026&DestApp=WOS_CPL
ID情報
  • DOI : 10.1152/jn.00536.2007
  • ISSN : 0022-3077
  • PubMed ID : 17928563
  • Web of Science ID : WOS:000251775700026

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