Regulation of slow wave frequency by IP3-sensitive calcium release in the murine small intestine

Slow waves determine frequency and propagation characteristics of contracti ons in the small intestine, yet little is known about mechanisms of slow wa ve regulation. We propose a role for intracellular Ca2+, inositol 1,4,5,-tr isphosphate (IP3)-sensitive Ca2+ release, and sarcoplasmic reticulum (SR) C a2+ content in the regulation of slow wave frequency because 1) 1,2-bis(2-a minophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a cytosolic Ca2+ chelator , reduced the frequency or abolished the slow waves; 2) thapsigargin and cy clopiazonic acid (CPA), inhibitors of SR Ca2+-ATPase, decreased slow wave f requency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP 3-induced Ca2+ release, abolished slow wave activity; 4) caffeine and phosp holipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl-N,N-d iphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP3 synthesis with carbachol, norepinephrin e, or phenylephrine acting on alpha (1)-adrenoceptors initially increased s low wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP3 receptors increased slow wave fre quency, and 7) ryanodine, a selective modulator of Ca2+ induced Ca2+ releas e, had no effect on slow wave frequency. In summary, these data are consist ent with a role of IP3 sensitive Ca2+ release and the rate of SR Ca2+ refil ling in regulation of intestinal slow wave frequency.