title: Degenerin/epithelial Na+ channel proteins: components of a vascular mechanosensor.
abstract: Mechanosensitive ion channels are thought to mediate stretch-induced contraction in vascular smooth muscle cells (VSMCs); however, the molecular identity of the mechanosensitive ion channel complex is unknown. Although recent reports suggest degenerin/epithelial Na+ channel (DEG/ENaC) proteins may be mechanosensors in sensory neurons, their role as mechanosensors in vascular tissue has not been examined. We first tested whether DEG/ENaC subunits are expressed in cerebral blood vessels and VSMCs and then examined their role as mechanosensors in mediating the myogenic response in intact blood vessels. Using RT-PCR, we found ENaC transcripts expressed in rat cerebral arteries and freshly dissociated rat cerebral VSMCs. We also detected ENaC expression in isolated blood vessels and VSMCs by immunoblotting and immunolocalization. Moreover, inhibition of ENaC with amiloride (1 micromol/L) and benzamil (30 nmol/L, 1 micromol), an amiloride analog, blocked myogenic constriction in isolated rat cerebral arteries. These data suggest that DEG/ENaC proteins are required for vessel responses to pressure and are consistent with the evolutionary conservation of mechanosensory function of DEG/ENaC proteins.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. hdrummond@physiology.umsmed.edu
authors.forename: Heather A
authors.initials: HA
authors.lastname: Drummond
authors.forename: Debebe
authors.initials: D
authors.lastname: Gebremedhin
authors.forename: David R
authors.initials: DR
authors.lastname: Harder
mesh_terms: D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism*; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008465:Mechanoreceptors; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; C013407:benzamil; D000584:Amiloride