TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells.
To investigate the possible role of members of the mammalian transient receptor potential (TRP) channel family (TRPC1-7) in vasoconstrictor-induced Ca(2+) entry in vascular smooth muscle cells, we studied [Arg(8)]-vasopressin (AVP)-activated channels in A7r5 aortic smooth muscle cells. AVP induced an increase in free cytosolic Ca(2+) concentration ([Ca(2+)](i)) consisting of Ca(2+) release and Ca(2+) influx. Whole cell recordings revealed the activation of a nonselective cation current with a doubly rectifying current-voltage relation strikingly similar to those described for some heterologously expressed TRPC isoforms. The current was also stimulated by direct activation of G proteins as well as by activation of the phospholipase Cgamma-coupled platelet-derived growth factor receptor. Currents were not activated by store depletion or increased [Ca(2+)](i). Application of 1-oleoyl-2-acetyl-sn-glycerol stimulated the current independently of protein kinase C, a characteristic property of the TRPC3/6/7 subfamily. Like TRPC6-mediated currents, cation currents in A7r5 cells were increased by flufenamate. Northern hybridization revealed mRNA coding for TRPC1 and TRPC6. We therefore suggest that TRPC6 is a molecular component of receptor-stimulated Ca(2+)-permeable cation channels in A7r5 smooth muscle cells.
Jung
Silke
S
Institut für Pharmakologie, Freie Universität Berlin, 14195 Berlin, Germany.
Strotmann
Rainer
R
Schultz
Günter
G
Plant
Tim D
TD
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D015152:Blotting, Northern; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling; D002412:Cations / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D004553:Electric Conductivity; D004594:Electrophysiology; D005439:Flufenamic Acid / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D050052:TRPC Cation Channels
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002412:Cations; D007093:Imidazoles; D007473:Ion Channels; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D001127:Arginine Vasopressin; D005439:Flufenamic Acid; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium