title: Swelling-activated cation channels mediate depolarization of rat cerebrovascular smooth muscle by hyposmolarity and intravascular pressure.
abstract: 1. Increases in intravascular pressure depolarize vascular smooth muscle cells. Based on the attenuating effects of Cl- channel antagonists, it has been suggested that swelling-activated Cl- channels may be integral to this response. Consequently, this study tested for the presence of a swelling-activated Cl- conductance in both intact rat cerebral arteries and isolated rat smooth muscle cells. 2. A 50 mosmol l-1 hyposmotic challenge (300 to 250 mosmol l-1) constricted rat cerebral arteries. This constriction contained all the salient features of a pressure-induced response including smooth muscle cell depolarization and a rise in intracellular Ca2+ that was blocked by voltage-operated Ca2+ channel antagonists. The hyposmotically induced depolarization was attenuated by DIDS (300 microM) and tamoxifen (1 microM), a response consistent with the presence of a swelling-activated Cl- conductance. 3. A swelling-activated current was identified in cerebral vascular smooth muscle cells. This current was sensitive to Cl- channel antagonists including DIDS (300 microM), tamoxifen (1 microM) and IAA-94 (100 microM). However, contrary to expectations, the reversal potential of this swelling-activated current shifted with the Na+ equilibrium potential and not the Cl- equilibrium potential, indicating that the swelling-activated current was carried by cations and not anions. The swelling-activated cation current was blocked by Gd3+, a cation channel antagonist. 4. Gd3+ also blocked both swelling- and pressure-induced depolarization of smooth muscle cells in intact cerebral arteries. 5. These findings suggest that swelling- and pressure-induced depolarization arise from the activation of a cation conductance. This current is inhibited by DIDS, tamoxifen, IAA-94 and gadolinium.
authors.affiliation: Department of Pharmacology, University of Vermont, Burlington, VT 05405, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Welsh
authors.forename: M T
authors.initials: MT
authors.lastname: Nelson
authors.forename: D M
authors.initials: DM
authors.lastname: Eckman
authors.forename: J E
authors.initials: JE
authors.lastname: Brayden
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D004553:Electric Conductivity; D005682:Gadolinium / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002412:Cations; D018118:Chloride Channels; D007473:Ion Channels; D013629:Tamoxifen; D012964:Sodium; D005682:Gadolinium