The effect of high [K+]o on spontaneous Ca2+ waves in freshly isolated interstitial cells of Cajal from the rabbit urethra

• Published in: Physiological reports Vol. 2; no. 1
• Main Authors: Drumm, Bernard T., Sergeant, Gerard P., Hollywood, Mark A., Thornbury, Keith T., Matsuda, Toshio T., Baba, Akemichi, Harvey, Brian J., McHale, Noel G.
• Format: Journal Article
• Language: English
• Published: Wiley Periodicals, Inc 21.01.2014
• Subjects: Calcium oscillations; interstitial cell of Cajal; Original Research; smooth muscle; sodium/calcium exchange
• ISSN: 2051-817X
• DOI: 10.1002/phy2.203

Interstitial cells of Cajal (ICC) act as putative pacemaker cells in the rabbit urethra. Pacemaker activity in ICC results from spontaneous global Ca2+ 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 [Ca2+] 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 [Ca2+]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 [Ca2+]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 Ca2+ channel blocker mibefradil (300 nmol/L). However, inhibition of Ca2+ 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 Ca2+ influx through reverse‐mode NCX. e00203 Pacemaker activity in ICC results from spontaneous global Ca2+ waves that can be increased in frequency by raising external [K+]. The experiments described support the hypothesis that high K+ solution increases the frequency of calcium waves in ICC by increasing Ca2+ influx through reverse‐mode NCX.