Regulation of slow wave frequency by IP3-sensitive calcium release in the murine small intestine
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abstract
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 Ca2+, inositol 1,4,5,-trisphosphate (IP3)-sensitive Ca2+release, and sarcoplasmic reticulum (SR) Ca2+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 Ca2+chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca2+-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP3-induced Ca2+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 IP3synthesis with carbachol, norepinephrine, or phenylephrine acting on α1-adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP3receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca2+-induced Ca2+release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP3-sensitive Ca2+release and the rate of SR Ca2+refilling in regulation of intestinal slow wave frequency.
