Action potential generation, Kit receptor immunohistochemistry and morphology of steel‐Dickie (Sl/Sld) mutant mouse small intestine

Neurogastroenterology and Motility - Tập 10 Số 1 - Trang 11-26 - 1998
H B Mikkelsen1, J Malysz, J D Huizinga, L Thuneberg
1Institute of Medical Anatomy, University of Copenhagen, Denmark. [email protected]

Tóm tắt

In contrast to wild‐type mice, homozygotes with mutations of the W locus do not express the functional Kit receptor and are severely deficient in the Auerbach's plexus (AP)‐associated subtype of interstitial cells of Cajal (ICC‐AP). With a morphologically intact neural and muscular structure, the absence in these mutants of both small‐intestinal slow waves and ICC‐AP constitutes strong evidence for a key role of ICC‐AP as pacemaker cells. In steel‐Dickie mutant mice (Sl/Sld), the gene coding for the Kit ligand (stem cell factor) is defective. We examined Sl/Sld mutants and controls with intracellular microelectrode techniques, combined with light and electron microscopy. The absence of the normal Kit ligand (Sl/Sld mice) had very similar effects as the absence of the Kit receptor in viable mice, mutated at the White spotting, W, locus (W/Wv mice), in that neither slow waves, nor Kit receptor immunoreactivity in the region of Auerbach's plexus nor ICC‐AP were present in the small intestine. In the Sl/Sld mouse, the smooth muscle cells generated action potentials at variable frequencies from a depolarized cell membrane of – 40 to – 55 mV. Increasing excitability by K channel blockers created many different patterns of action potential generation and the frequency increased from ∼ 16 cpm to 66 cpm. This was in sharp contrast to control mice where action potentials were always restricted to the plateau phase of the slow waves and the slow wave frequency remained constant at ∼ 39 cpm. Our data provide further strong support for the identification of ICC‐AP as small‐intestinal pacemaker cells. In addition, they provide a basis for the understanding of intestinal motor function without pacemaker activity.

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Tài liệu tham khảo

10.1016/0092-8674(91)90326-T

10.1038/335088a0

10.1016/0092-8674(90)90303-V

10.1016/S0065-2660(08)60549-0

10.1016/0092-8674(90)90302-U

10.1242/dev.116.2.369

10.1038/373347a0

Malysz J, 1996, Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal, Am J Physiol, 271, G387

10.1113/jphysiol.1994.sp020343

10.1007/978-3-642-68417-3_1

Thuneberg L, 1995, Deficiency of one type of interstitial cells of Cajal (ICC) and abscence of slow wave activity in the small intestine of Sl/Sld mouse mutants, Neurogastroenterol Motil, 7, 290

10.1152/ajpcell.1995.269.6.C1577

10.1007/BF00318744

10.1007/BF00315852

10.1007/BF00318222

10.1002/ar.1092130111

10.1139/y95-208

10.1152/ajplegacy.1975.229.5.1287

10.1113/jphysiol.1991.sp018779

10.1113/jphysiol.1992.sp019304

Torihashi S, 1995, c‐kit‐Dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract, Cell Tissue Res, 280, 97

Liu L W C, 1995, Simultaneous development of pacemaker activity and interstitial cells of Cajal network in neonatal mouse small intestine, Neurogastroenterol Motil, 7, 270

10.1128/MCB.15.12.6953

10.1007/BF01970006

Malysz J, 1996, Effects of voltage changes on pacemaker activity generated by smooth muscle cells and by interstitial cells of Cajal, Dig Dis Sci, 41, 1895

Liu L W C, 1995, Cyclopiazonic acid, inhibiting the endoplasmic reticulum calcium pump, reduces the canine colonic pacemaker frequency, J Pharmacol Exp Ther, 275, 1058

Huizinga J D, 1995, Action potentials and contractions in vivo do not propagate in the small intestine of the W/Wv mouse that lacks myenteric interstitial cells of Cajal, Neurogastroenterol Motil, 7, 263

10.1113/jphysiol.1993.sp019868

10.1007/BF02231728

Handbook of Physiology – the Gastrointestinal System I.Bethesda: American Physiology Society 1989: 349–86.

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Neurogastroenterology and Motility

Tập 10 Số 1

11-26

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