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Originally published In Press as doi:10.1074/jbc.M201728200 on March 15, 2002

J. Biol. Chem., Vol. 277, Issue 21, 19191-19197, May 24, 2002
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Calcium Oscillation Linked to Pacemaking of Interstitial Cells of Cajal
REQUIREMENT OF CALCIUM INFLUX AND LOCALIZATION OF TRP4 IN CAVEOLAE*

Shigeko TorihashiDagger §, Toyoshi FujimotoDagger , Claudia Trost, and Shinsuke Nakayama||

From the Departments of Dagger  Anatomy and Cell Biology and || Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan and the  Institute für Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany

Interstitial cells of Cajal (ICC) are considered to be pacemaker cells in gastrointestinal tracts. ICC generate electrical rhythmicity (dihydropyridine-insensitive) as slow waves and drive spontaneous contraction of smooth muscles. Although cytosolic Ca2+ has been assumed to play a key role in pacemaking, Ca2+ movements in ICC have not yet been examined in detail. In the present study, using cultured cell clusters isolated from mouse small intestine, we demonstrated Ca2+ oscillations in ICC. Fluo-4 was loaded to the cell cluster, the relative amount of cytosolic Ca2+ was recorded, and ICC were identified by c-Kit immunoreactivity. We specifically detected Ca2+ oscillation in ICC in the presence of dihydropyridine, which abolishes Ca2+ oscillation in smooth muscles. The oscillation was coupled to the electrical activity corresponding to slow waves, and it depended on Ca2+ influx through a non-selective cation channel, which was SK&F 96365-sensitive and store-operated. We further demonstrated the presence of transient receptor potential-like channel 4 (TRP4) in caveolae of ICC. Taken together, the results infer that the Ca2+ oscillation in ICC is intimately linked to the pacemaker function and depends on Ca2+ influx mediated by TRP4.


* This work was supported by the Ministry of Education, Science, Sports, and Culture of Japan and by the Japan Clinical Study Group for the Esophago-cardiac Region. A preliminary account was presented at the 18th International Symposium on Gastrointestinal Motility, November 15-19, 2001, Madison, WI (Torihashi, S., Fujimoto, T., and Nakayama, S. (2001) Neurogastroenterol. Motil. 13, 437a).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Dept. of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan. Tel.: 81-52-744-2001; Fax: 81-52-744-2012; E-mail: storiha@med.nagoya-u.ac.jp.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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