Diphosphate regulation of adenosine triphosphate sensitive potassium channel in human bladder smooth muscle cells

Shunichi Kajioka, Nouval Shahab, Haruhiko Asano, Hiromitsu Morita, Megumi Sugihara, Fumi Takahashi-Yanaga, Tatsuya Yoshihara, Shinsuke Nakayama, Narihito Seki, Seiji Naito

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Abstract

Purpose: To clarify the properties of adenosine triphosphate sensitive K+ channel in human detrusor smooth muscle we examined the effect of the representative nicotinic acid derivatives β-nicotinamide adenine dinucleotide, cyclic adenosine diphosphate ribose and nicotinic acid adenine dinucleotide phosphate (Sigma-Aldrich®) on human detrusor adenosine triphosphate sensitive K+ channels. Materials and Methods: Patch clamp procedures were done in human detrusor cells. Reverse transcriptase and real-time polymerase chain reaction were performed to clarify the subunit components of adenosine triphosphate sensitive K+ channels. Results: The K+ channel opener levcromakalim induced a long lasting outward current that was inhibited by glibenclamide (Sigma-Aldrich) under the whole cell configuration. The single channel study revealed that the unitary conductance of the adenosine triphosphate sensitive K+ channel in the human detrusor was 11 pS and nucleotide diphosphates increased its open probability. Applying β-nicotinamide adenine dinucleotide also activated the adenosine triphosphate sensitive K+ channel but applying cyclic adenosine diphosphate ribose or nicotinic acid adenine dinucleotide phosphate had little effect on channel activation. Molecular studies indicated that Kir6.1 and SUR2B were the predominant components of the adenosine triphosphate sensitive K + channel in the human detrusor. Conclusions: To our knowledge we report the first single channel study of the adenosine triphosphate sensitive K+ channel in the human detrusor. The properties of this channel, ie unitary conductance, adenosine triphosphate sensitivity and diphosphate activation, were consistent with those of other smooth muscle organs. β-Nicotinamide adenine dinucleotide has the potency to activate adenosine triphosphate sensitive K+ channels in the human detrusor. This channel likely has some role during ischemic conditions as well as physiological muscle motion leading to the activation of cell metabolism.

Original languageEnglish
Pages (from-to)736-744
Number of pages9
JournalJournal of Urology
Volume186
Issue number2
DOIs
Publication statusPublished - Aug 1 2011

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All Science Journal Classification (ASJC) codes

  • Urology

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