Levcromakalim and MgGDP activate small conductance ATP-sensitive K + channels of K+ channel pore 6.1/sulfonylurea receptor 2A in pig detrusor smooth muscle cells: Uncoupling of cAMP signal pathways

Shunichi Kajioka, Shinsuke Nakayama, Haruhiko Asano, Narihito Seki, Seiji Naito, Alison F. Brading

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Pharmacological studies have suggested the existence of ATP-sensitive K+ (KATP) channel as a therapeutic target in urinary bladders; however, electrical properties have not yet been shown. Patch-clamp techniques were applied to investigate the properties of KATP channels in pig detrusor cells. In whole-cell configuration, levcromakalim, a KATP channel opener, induced a long-lasting outward current in a concentration-dependent manner. The current-voltage curve of the levcromakalim-induced membrane current intersected at approximately -80 mV. This current was abolished by glibenclamide. Intracellular application of 0.1 mM GDP significantly enhanced the levcromakalim-induced membrane current, whereas cAMP did not. Furthermore, neurotransmitters related to cAMP signaling, such as calcitonin gene-related peptide, vasointestinal peptide, adenosine, and somatostatin, had little effect on the membrane current. In cell-attached configuration, levcromakalim activated K+ channels with a unitary conductance of ∼12 pS. When the patch configuration was changed to inside-out mode, the K+ channel activity ran down. Subsequent application of 1 mM GDP reactivated the channels. The openings of the ∼12 pS K+ channels in the presence of 1 mM GDP was suppressed by ATP and glibenclamide. In reverse transcription-polymerase chain reaction, K+ channel pore 6.1 and sulfonylurea receptor (SUR)2A were predominant in pig detrusor cells. The 12 pS K+ channel activated by levcromakalim in pig detrusor smooth muscle cells is a KATP channel. The predominant expression of SUR2A can account for the lack of effect of neurotransmitters related to cAMP.

Original languageEnglish
Pages (from-to)114-123
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume327
Issue number1
DOIs
Publication statusPublished - Oct 2008

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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