Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 308, Issue 5, Pages G378-G388Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00308.2014
Keywords
interstitial cells of Cajal; NKCC1; pacemaker; slow wave; small intestine
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Funding
- 24th General Assembly of the Japanese Association of Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases [P01 DK41315]
- Grants-in-Aid for Scientific Research [26460912] Funding Source: KAKEN
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Slow waves (slow wavesICC) were recorded from myenteric interstitial cells of Cajal (ICC-MY) in situ in the rabbit small intestine, and their properties were compared with those of mouse small intestine. Rabbit slow wavesICC consisted of an upstroke depolarization followed by a distinct plateau component. Ni2+ and nominally Ca2+-free solutions reduced the rate-of-rise and amplitude of the upstroke depolarization. Replacement of Ca2+ with Sr2+ enhanced the upstroke component but decreased the plateau component of rabbit slow wavesICC. In contrast, replacing Ca2+ with Sr2+ decreased both components of mouse slow wavesICC. The plateau component of rabbit slow wavesICC was inhibited in low-extracellular-Cl- -concentration (low-[Cl-](0)) solutions and by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl- channels, cyclopiazonic acid (CPA), an inhibitor of internal Ca2+ pumps, or bumetanide, an inhibitor of Na+-K+-2Cl(-) cotransporter (NKCC1). Bumetanide also inhibited the plateau component of mouse slow wavesICC. NKCC1-like immunoreactivity was observed mainly in ICC-MY in the rabbit small intestine. Membrane depolarization with a high-K+ solution reduced the upstroke component of rabbit slow wavesICC. In cells depolarized with elevated external K+, DIDS, CPA, and bumetanide blocked slow wavesICC. These results suggest that the upstroke component of rabbit slow wavesICC is partially mediated by voltage-dependent Ca2+ influx, whereas the plateau component is dependent on Ca2+-activated Cl- efflux. NKCC1 is likely to be responsible for Cl- accumulation in ICC-MY. The results also suggest that the mechanism of the upstroke component differs in rabbit and mouse slow wavesICC in the small intestine.
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