Intracellular nucleotide‐mediated gating of SUR/Kir6.0 complex potassium channels expressed in a mammalian cell line and its modification by pinacidil

• Eisaku Satoh

• Mitsuhiko Yamada

• Chikako Kondo

• Vez P. Repunte

• Yoshiyuki Horio

• Toshihiko Iijima

• Yoshihisa Kurachi

抄録

<jats:list list-type="explicit-label"> We have examined the properties of intracellular nucleotide‐mediated gating of K + channel constructs composed of the sulphonylurea receptor 2B and the inwardly rectifying K + channel subunits Kir6.1 and Kir6.2 (SUR2B/Kir6.1 and SUR2B/Kir6.2 complex K + channels) heterologously expressed in human embryonic kidney (HEK) 293T cells. In the cell‐attached form, both types of K + channel were activated by pinacidil. In inside‐out (IO) patches, the SUR2B/Kir6.2 channels opened spontaneously and were inhibited by intracellular ATP (ATP i ). Pinacidil attenuated the ATP i ‐mediated channel inhibition in a concentration‐dependent manner. In contrast, the SUR2B/Kir6.1 channels required intracellular nucleoside di‐ or tri‐, but not mono‐, phosphates for opening. The potency of adenine, guanine or uracil nucleotides to activate SUR2B/Kir6.1 channels was enhanced by pinacidil. In the presence of pinacidil, adenine and guanine, but not uracil, nucleotides exhibited bell‐shaped concentration‐dependent activating effects on SUR2B/Kir6.1 channels. This was due to channel inhibition caused by adenine and guanine nucleotides, which was unaffected by pinacidil. From power density spectrum analysis of SUR2B/Kir6.1 currents, channel activation could be described by the product of two gates, a nucleotide‐independent fast channel gate and a nucleotide‐dependent slow gate, which controlled the number of functional channels. Pinacidil specifically increased the potency of nucleotide action on the slow gate. We conclude that Kir6.0 subunits play a crucial role in the nucleotide‐mediated gating of SUR/Kir6.0 complex K + channels and may determine the molecular mode of pinacidil action.

収録刊行物

• The Journal of Physiology

  The Journal of Physiology 511 (3), 663-674, 1998-09

  Wiley

キーワード

• Physiology

詳細情報

• CRID: 1364233268670226432
• NII論文ID: 30022488713
• DOI: 10.1111/j.1469-7793.1998.663bg.x
• ISSN: 14697793
• ISSN: 00223751
• ISSN: http://id.crossref.org/issn/00223751
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1469-7793.1998.663bg.x
• Web Site: https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-7793.1998.663bg.x
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