Regulation of slow wave frequency by IP 3 -sensitive calcium release in the murine small intestine

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 280; no. 3; pp. G439 - G448
• Main Authors: Malysz, John, Donnelly, Graeme, Huizinga, Jan D.
• Format: Journal Article
• Language: English
• Published: 01.03.2001
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.2001.280.3.G439

Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca 2+ , inositol 1,4,5,-trisphosphate (IP 3 )-sensitive Ca 2+ release, and sarcoplasmic reticulum (SR) Ca 2+ content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid-AM, a cytosolic Ca 2+ chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca 2+ -ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP 3 -induced Ca 2+ release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl- N, N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP 3 synthesis with carbachol, norepinephrine, or phenylephrine acting on α 1 -adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP 3 receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca 2+ -induced Ca 2+ release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP 3 -sensitive Ca 2+ release and the rate of SR Ca 2+ refilling in regulation of intestinal slow wave frequency.