title: The Na+/Ca2+ exchanger inhibitor, KB-R7943, blocks a nonselective cation channel implicated in chemosensory transduction.
abstract: The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a nonselective sodium-gated cation (SGC) channel, a presumptive transient receptor potential (TRP)C channel homolog, plays a crucial role in olfactory transduction, at least in part by amplifying the primary transduction current. To better determine the functional role of the channel, it is important to selectively block the channel independently of other elements of the transduction cascade, causing us to search for specific pharmacological blockers of the SGC channel. Given evidence that the Na(+)/Ca(2+) exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we studied this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both inside- and outside-out patch recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the channel open probability without changing single channel amplitude. KB-R7943 also reversibly and in a dose-dependent manner inhibited both the odorant-evoked discharge of lobster ORNs and the odorant-evoked whole cell current. Our findings strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely does so directly and not through its ability to block the Na(+)/Ca(2+) exchanger.
authors.affiliation: Whitney Laboratory for Marine Bioscience, Center for Smell and Taste, McKnight Brain Institute, University of Florida, Gainesville, FL, USA. pezier@whitney.ufl.edu
authors.forename: A
authors.initials: A
authors.lastname: Pezier
authors.forename: Y V
authors.initials: YV
authors.lastname: Bobkov
authors.forename: B W
authors.initials: BW
authors.lastname: Ache
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000187:drug effects*; D033521:Palinuridae; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D050052:TRPC Cation Channels / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D001593:Benzyl Compounds; D019831:Sodium-Calcium Exchanger; D050052:TRPC Cation Channels; D053778:Thiazolidines; D013890:Thiourea