title: Molecular expression and functional role of canonical transient receptor potential channels in airway smooth muscle cells.
abstract: Multiple canonical or classic transient receptor potential (TRPC) molecules are expressed in animal and human airway smooth muscle cells (SMCs). TRPC3, but not TRPC1, is a major molecular component of native non-selective cation channels (NSCCs) to contribute to the resting [Ca(2+)](i) and muscarinic increase in [Ca(2+)](i) in freshly isolated airway SMCs. TRPC3-encoded NSCCs are significantly increased in expression and activity in airway SMCs from ovalbumin-sensitized/challenged "asthmatic" mice, whereas TRPC1-encoded channel activity, but not its expression, is largely augmented. The upregulated TRPC3- and TRPC1-encoded NSCC activity both mediate "asthmatic" membrane depolarization in airway SMCs. Supportively, tumor necrosis factor-α (TNFα), an important asthma mediator, increases TRPC3 expression, and TRPC3 gene silencing inhibits TNFα-mediated augmentation of acetylcholine-evoked increase in [Ca(2+)](i) in passaged airway SMCs. In contrast, TRPC6 gene silencing has no effect on 1-oleoyl-2-acetyl-sn-glycerol (OAG)-evoked increase in [Ca(2+)](i) in primary isolated cells. These findings provide compelling information indicating that TRPC3-encoded NSCCs are important for physiological and pathological cellular responses in airway SMCs. However, continual studies are necessary to further determine whether, which, and how TRPC-encoded channels are involved in cellular responses in normal and diseased (e.g., asthmatic) airway SMCs.
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. wangy@mail.amc.edu
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Wang
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D017136:Ion Transport; D008564:Membrane Potentials; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000502:physiology*
chemical_list: D050051:Transient Receptor Potential Channels; D002118:Calcium