TRPC4 is an essential component of the nonselective cation channel activated by muscarinic stimulation in mouse visceral smooth muscle cells.
Classical transient receptor potential channels (TRPCs) are thought to be candidates for the nonselective cation channels (NSCCs) involved in pacemaker activity and its neuromodulation in murine stomach smooth muscle. We aimed to determine the role of TRPC4 in the formation of NSCCs and in the generation of slow waves. At a holding potential of -60 mV, 50 mM carbachol (CCh) induced INSCC of amplitude [500.8+/-161.8 pA (n=8)] at -60 mV in mouse gastric smooth muscle cells. We investigated the effects of commercially available antibodies to TRPC4 on recombinant TRPC4 expressed in HEK cells and CCh-induced NSCCs in gastric smooth muscle cells. TRPC4 currents in HEK cells were reduced from 1525.6+/-414.4 pA (n=8) to 146.4+/-83.3 pA (n=10) by anti-TRPC4 antibody and INSCC amplitudes were reduced from 230.9+/-36.3 pA (n=15) to 49.8+/-11.8 pA (n=9). Furthermore, INSCC in the gastric smooth muscle cells of TRPC4 knockout mice was only 34.4+/-10.4 pA (n=8) at -60 mV. However, slow waves were still present in the knockout mice. Our data suggest that TRPC4 is an essential component of the NSCC activated by muscarinic stimulation in the murine stomach.
Lee
Kyu Pil
KP
Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul 110-799, Korea.
Jun
Jae Yeoul
JY
Chang
In-Youb
IY
Suh
Suk-Hyo
SH
So
Insuk
I
Kim
Ki Whan
KW
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D004553:Electric Conductivity; D005753:Gastric Mucosa / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*
D002412:Cations; D018679:Cholinergic Agonists; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D002217:Carbachol