Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease.
The apamin-sensitive component of the inhibitory response of the gastrointestinal musculature involves the small conductance Ca(2+)-activated K(+) channel SK3. Kit-immunoreactive (ir) interstitial cells of Cajal appear to be involved in nitrergic inhibition while the role of the recently described CD34-ir fibroblast-like cells adjacent to, but distinct from, the cells of Cajal remains elusive. The distribution of SK3 was studied by immunohistochemistry in the normal human gut, in motility disorders with a lack of cells of Cajal (infantile hypertrophic pyloric stenosis and Hirschsprung's disease) and in mice deficient in cells of Cajal. SK3 immunoreactivity was observed exclusively in Kit-negative interstitial cells adjacent to, but distinct from, the Kit-ir interstitial cells of Cajal in the normal gut. The distribution of SK3-ir cells was not altered in conditions where cells of Cajal were lacking. These cells were CD34-ir fibroblast-like cells in the human gut and in the mouse stomach, while SK3-ir cells in the mouse intestine were CD34 negative. As SK channels are reportedly involved in inhibitory neurotransmission, our morphological observations suggest that SK3-ir interstitial cells, distinct from the Kit-ir interstitial cells of Cajal, may represent a novel cellular component in the control of excitability of the digestive musculature. Further studies will be required to directly address the function of these cells.
Vanderwinden
Jean-Marie
JM
Laboratoire de Neurophysiologie, Faculté de Médecine, Université Libre de Bruxelles, Campus Erasme, CP 601, 808 route de Lennik, 1070 Brussels, Belgium. jmvdwin@ulb.ac.be
Rumessen
Jüri J
JJ
de Kerchove d'Exaerde
Alban
A
Gillard
Karine
K
Panthier
Jean-Jacques
JJ
de Laet
Marc-Henri
MH
Schiffmann
Serge N
SN
D000293:Adolescent; D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004068:Digestive System Physiological Phenomena; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006627:Hirschsprung Disease / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology* / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000235:genetics / Q000503:physiopathology; D051640:Small-Conductance Calcium-Activated Potassium Channels
D018952:Antigens, CD34; C406328:KCNN3 protein, human; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D019009:Proto-Oncogene Proteins c-kit