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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
Calcium Oscillation Linked to Pacemaking of
Interstitial Cells of Cajal
REQUIREMENT OF CALCIUM INFLUX AND LOCALIZATION OF TRP4 IN
CAVEOLAE*
Shigeko
Torihashi §,
Toyoshi
Fujimoto ,
Claudia
Trost¶, and
Shinsuke
Nakayama
From the Departments of 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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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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