Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity.
OBJECTIVE
Interstitial cells of Cajal are pacemakers in the gastrointestinal tract, regulating rhythmicity by activating nonselective cation channels. In Caenorhabditis elegans, the melastatin-type transient receptor potential (TRPM) channel, especially TRPM7, was suggested as being involved in defecation rhythm. The aim here was to show that the nonselective cation channel in interstitial cells of Cajal in mouse small intestine has properties essentially identical to those of murine TRPM7, heterologously expressed in human embryonic kidney cells.


METHODS
The patch-clamp technique for whole-cell recording was used in cultured or single interstitial cells of Cajal. TRPM7-specific small interfering RNAs were used for specific inhibition of TRPM7.


RESULTS
Electrophysiological and pharmacological properties of the nonselective cation channel in interstitial cells of Cajal were the same as those of TRPM7. Reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry all showed abundant and localized expression of TRPM7 messenger RNA and protein in mouse small intestine. Treatment of primary cultured interstitial cells of Cajal with TRPM7-specific small interfering RNA resulted in inhibition of pacemaking activity.


CONCLUSIONS
TRPM7 is required for intestinal pacemaking. The protein is a likely potential target for pharmacological treatment of motor disorders of the gut.
Kim
Byung Joo
BJ
Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul, Korea.
Lim
Hyun-Ho
HH
Yang
Dong Ki
DK
Jun
Jae Yeoul
JY
Chang
In Youb
IY
Park
Chul-Seung
CS
So
Insuk
I
Stanfield
Peter R
PR
Kim
Ki Whan
KW
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002413:Cations, Divalent / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007422:Intestines / Q000294:innervation / Q000502:physiology; D007668:Kidney / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels / Q000235:genetics / Q000502:physiology*
D002413:Cations, Divalent; D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse