Abstract
Interstitial cells of Cajal (ICCs) generate the electrical pacemaker activity (slow wave) of gastrointestinal muscles. Slow waves propagate within ICC networks, conduct into smooth muscle cells through gap junctions, and initiate phasic contractions by activating Ca2+ entry through L-type Ca2+ channels. Pacemaker activity in the murine small intestine is due mainly to a periodic activation of the nonselective cation channel(NSCC) in ICCs. The Drosophila transient receptor potential (TRP) channels and their mammalian homologues are thought to encode a diverse group of Ca2+-permeable nonselective cation channels. However, there is little direct evidence linking mammalian TRP proteins with NSCC in ICCs. Here we show that NSCC in ICCs in mouse small intestine has essentially identical properties to those of murine TRPM7 heterologously expressed in HEK cells. Electrophysiological and pharmacological properties of NSCC in ICCs were the same as those of TRPM7. The reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry all showed abundant and localized expression of both TRPM7 mRNA and protein in mouse small intestine and the treatment of primary cultured ICCs with TRPM7-specific small interfering RNA resulted in an inhibition of pacemaking activity in cultured ICCs. These results show that TRPM7 is a primary molecular candidate for NSCC regulating the pacemaking activity of gastrointestinal tract. The protein is a likely target for pharmacological treatment of motor disorders of the gut. [Jpn J Physiol 55 Suppl:S51 (2005)]
