title: The effect of high [K(+)]o on spontaneous Ca(2+) waves in freshly isolated interstitial cells of Cajal from the rabbit urethra.
abstract: Interstitial cells of Cajal (ICC) act as putative pacemaker cells in the rabbit urethra. Pacemaker activity in ICC results from spontaneous global Ca(2+) waves that can be increased in frequency by raising external [K(+)]. The purpose of this study was to elucidate the mechanism of this response. Intracellular [Ca(2+)] was measured in fluo-4-loaded smooth muscle cells (SMCs) and ICC using a Nipkow spinning disk confocal microscope. Increasing [K(+)]o to 60 mmol/L caused an increase in [Ca(2+)]i accompanied by contraction in SMCs. Raising [K(+)]o did not cause contraction in ICC, but the frequency of firing of spontaneous calcium waves increased. Reducing [Ca(2+)]o to 0 mmol/L abolished the response in both cell types. Nifedipine of 1 μmol/L blocked the response of SMC to high [K(+)]o, but did not affect the increase in firing in ICC. This latter effect was blocked by 30 μmol/L NiCl2 but not by the T-type Ca(2+) channel blocker mibefradil (300 nmol/L). However, inhibition of Ca(2+) influx via reverse-mode sodium/calcium exchange (NCX) using either 1 μmol/L SEA0400 or 5 μmol/L KB-R7943 did block the effect of high [K(+)]o on ICC. These data suggest that high K(+) solution increases the frequency of calcium waves in ICC by increasing Ca(2+) influx through reverse-mode NCX.
authors.affiliation: Smooth Muscle Research Centre, Dundalk Institute of Technology, DundalkCo. Louth, Ireland ; Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Bernard T
authors.initials: BT
authors.lastname: Drumm
authors.affiliation: Smooth Muscle Research Centre, Dundalk Institute of Technology, DundalkCo. Louth, Ireland.
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Sergeant
authors.affiliation: Smooth Muscle Research Centre, Dundalk Institute of Technology, DundalkCo. Louth, Ireland.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hollywood
authors.affiliation: Smooth Muscle Research Centre, Dundalk Institute of Technology, DundalkCo. Louth, Ireland.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Thornbury
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Toshio T
authors.initials: TT
authors.lastname: Matsuda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.affiliation: Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Harvey
authors.affiliation: Smooth Muscle Research Centre, Dundalk Institute of Technology, DundalkCo. Louth, Ireland.
authors.forename: Noel G
authors.initials: NG
authors.lastname: McHale
keywords: Calcium oscillations; interstitial cell of Cajal; smooth muscle; sodium/calcium exchange
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