Role of K+ channels in regulating spontaneous activity in the muscularis mucosae of guinea pig bladder

Ken Lee, Ayu Isogai, Minori Antoh, Shunichi Kajioka, Masatoshi Eto, Hikaru Hashitani

Research output: Contribution to journalArticle

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Abstract

To explore the roles of various K+ channels in regulating the spontaneous activity of bladder muscularis mucosae (MM) that is considered to play an important role in maintaining mucosal function. Effects of K+ channel modulators on electrical and contractile activity in the guinea-pig bladder MM were examined using intracellular microelectrode and isometric tension recording. The MM predominately generated bursting spontaneous action potentials (SAPs) and phasic contractions (SPCs) that were blocked by nifedipine (1 µM). NS309 (10 µM), a small-conductance Ca2+-activated K+ (SK) channel opener, dramatically prolonged after-hyperpolarisation (AHP) and converted bursting SAPs into individually action potentials in an apamin (100 nM)-sensitive manner. Apamin alone increased the number of SAPs during bursts. NS1619 (10 µM), a large-conductance Ca2+-activated K+ (BK) channel opener, abolished SAPs in a manner reversed by iberiotoxin (IbTX, 100 nM), a BK channel blocker. IbTX alone enlarged SAPs and abolished their AHPs. Flupirtine (10 µM), a voltage-dependent K+ channel (Kv7) opener, diminished SAPs in a manner reversed by XE991 (10 µM), a Kv7 channel blocker. XE991 alone exerted modest excitatory effects on SAPs. These K+ channel modulators had corresponding effects on SPCs. Bursting SAP firing appears to result from a lower level activation of SK channels in MM than that DSM. BK channels play a predominant role in regulating SAP configuration, while Kv7 channels have only a marginal role. The prevention of bursting SAPs and associated reduction in SPCs upon the pharmacological activation of a reserved population of SK channels may well have a considerable therapeutic potential.

Original languageEnglish
Pages (from-to)30-37
Number of pages8
JournalEuropean Journal of Pharmacology
Volume818
DOIs
Publication statusPublished - Jan 5 2018

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Action Potentials
Guinea Pigs
Mucous Membrane
Urinary Bladder
Large-Conductance Calcium-Activated Potassium Channels
Apamin
Calcium-Activated Potassium Channels
flupirtine
Microelectrodes
Nifedipine
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Role of K+ channels in regulating spontaneous activity in the muscularis mucosae of guinea pig bladder. / Lee, Ken; Isogai, Ayu; Antoh, Minori; Kajioka, Shunichi; Eto, Masatoshi; Hashitani, Hikaru.

In: European Journal of Pharmacology, Vol. 818, 05.01.2018, p. 30-37.

Research output: Contribution to journalArticle

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