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Abstract
Byung Joo Kim1, Hyun-Ho Lim2, Dong Ki Yang1, Jae Yeoul Jun3, In Youb Chang4, Chul-Seung Park2, Insuk So1, Peter R. Stanfield and Ki Whan Kim1
1Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul, Korea
2Dpartment of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea
3Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
4Department of Anatomy, College of Medicine, Chosun University, Gwangju, Korea
Department of Biological Sciences, University of Warwick, Coventry, United Kingdom
Background & Aims: 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.
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