title: On the potential role of source and species of diacylglycerol in phospholipase-dependent regulation of TRPC3 channels.
abstract: Members of the Transient Receptor Potential Canonical (TRPC) family of channel forming proteins are among the most important Ca(2+)-permeable cation channels in non-excitable cells. Physiologically, TRPC channels are activated downstream receptor-dependent stimulation of phospholipases, either by store-operated or non-store operated mechanisms. TRPC3, a member of the TRPC3/6/7 subfamily, has been largely studied mostly due to its ability to function in one or the other modes, depending on cell type and expression conditions. The role of TRPC3 as a non-store operated channel has been attributed to its ability to respond to diacylglycerol (DAG) either exogenously applied or endogenously produced following activation of receptor-stimulated phospholipases. Despite the vast amount of information accumulated on this topic, some critical aspects related to phospholipase-dependent DAG-mediated regulation of TRPC3 remain unclear and/or unexplored. Among these, the source and species of native DAG, modulation by different DAG-generating phospholipases and protein kinase C-dependent inhibition of TRPC3 in its native environment are just few examples. The present essay is intended to compile existing knowledge on the nature of phospholipase-derived DAGs, their biophysical properties and current evidence on phospholipase-dependent regulation of TRPC3, to speculate on potential scenarios that may eventually provide answers to some of the above questions.
authors.affiliation: Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, OH, USA Guillermo.Vazquez@ utoledo.edu
authors.forename: Guillermo
authors.initials: G
authors.lastname: Vazquez
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Tano
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smedlund
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000502:physiology*; D010740:Phospholipases / Q000502:physiology*; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D010740:Phospholipases; D002118:Calcium