Characterization of slow waves generated by myenteric interstitial cells of Cajal of the rabbit small intestine

Am J Physiol Gastrointest Liver Physiol. 2015 Mar 1;308(5):G378-88. doi: 10.1152/ajpgi.00308.2014. Epub 2014 Dec 24.

Abstract

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. Ni(2+) and nominally Ca(2+)-free solutions reduced the rate-of-rise and amplitude of the upstroke depolarization. Replacement of Ca(2+) with Sr(2+) enhanced the upstroke component but decreased the plateau component of rabbit slow wavesICC. In contrast, replacing Ca(2+) with Sr(2+) decreased both components of mouse slow wavesICC. The plateau component of rabbit slow wavesICC was inhibited in low-extracellular-Cl(-)-concentration (low-[Cl(-)]o) solutions and by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl(-) channels, cyclopiazonic acid (CPA), an inhibitor of internal Ca(2+) 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 Ca(2+) influx, whereas the plateau component is dependent on Ca(2+)-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.

Keywords: NKCC1; interstitial cells of Cajal; pacemaker; slow wave; small intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Female
  • Interstitial Cells of Cajal / drug effects
  • Interstitial Cells of Cajal / metabolism
  • Interstitial Cells of Cajal / physiology*
  • Intestine, Small / cytology
  • Intestine, Small / physiology*
  • Male
  • Membrane Potentials
  • Membrane Transport Modulators / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Myenteric Plexus / cytology
  • Myenteric Plexus / physiology*
  • Rabbits
  • Solute Carrier Family 12, Member 2 / genetics
  • Solute Carrier Family 12, Member 2 / metabolism
  • Species Specificity

Substances

  • Membrane Transport Modulators
  • Solute Carrier Family 12, Member 2