title: A derivative of amiloride blocks both the light-regulated and cyclic GMP-regulated conductances in rod photoreceptors.
abstract: Vertebrate rod photoreceptors in the dark maintain an inward current across the outer segment membrane. The photoresponse results from a light-induced suppression of this dark current. The light-regulated current is not sensitive to either tetrodotoxin or amiloride, potent blockers of Na+ channels. Here, we report that a derivative of amiloride, 3',4'-dichlorobenzamil (DCPA), completely suppresses the dark current and light response recorded from rod photoreceptors. DCPA also blocks a cyclic GMP-activated current in excised patches of rod plasma membrane and a cGMP-induced Ca++ flux from rod disk membranes. These results are consistent with the notion that the Ca++ flux mechanism in the disk membrane and the light-regulated conductance in the plasma membrane are identical. DCPA also inhibits the Na/Ca exchange mechanism in intact rods, but at a 5-10-fold-higher concentration than is required to block the cGMP-activated flux and current. The blocking action of DCPA in 10 nM Ca++ is different from that in 1 mM Ca++, which suggests either that the conductance state of the light-regulated channel may be modified in high and low concentrations of Ca++, or that there may be two ionic channels in the rod outer segment membrane.
authors.affiliation: Laboratory of Molecular Biology, University of Wisconsin, Madison 53706.
authors.forename: G D
authors.initials: GD
authors.lastname: Nicol
authors.forename: P P
authors.initials: PP
authors.lastname: Schnetkamp
authors.forename: Y
authors.initials: Y
authors.lastname: Saimi
authors.forename: E J
authors.initials: EJ
authors.lastname: Cragoe
authors.forename: M D
authors.initials: MD
authors.lastname: Bownds
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006152:Cyclic GMP / Q000502:physiology*; D066298:In Vitro Techniques; D008027:Light; D009431:Neural Conduction / Q000187:drug effects*; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000502:physiology; D011892:Rana catesbeiana; D012374:Rod Cell Outer Segment / Q000378:metabolism
chemical_list: C041470:3',4'-dichlorobenzamil; D000584:Amiloride; D006152:Cyclic GMP; D002118:Calcium