title: Silver ions induce a rapid Ca2+ release from isolated intact bovine rod outer segments by a cooperative mechanism.
abstract: Micromolar concentrations of silver ion activate large Ca2+ fluxes across the plasma membrane of intact rod outer segments isolated from bovine retinas (intact ROS). The rate of Ag+-induced Ca2+ efflux from intact ROS depended on the Ag+ concentration in a sigmoidal manner suggesting a cooperative mechanism with a Hill coefficient between 2 and 3. At a concentration of 50 microM Ag+ the rate of Ca2+ efflux was 7 x 10(6) Ca2+/outer segment/sec; this represents a change in total intracellular Ca2+ by 0.7 mM/outer segment/sec. Addition of the nonselective ionophore gramicidin in the absence of external alkali cations greatly reduced the Ag+-induced Ca2+ efflux from intact ROS, apparently by enabling internal alkali cations to leak out. Adding back alkali cations to the external medium restored Ag+-induced Ca2+ efflux when gramicidin was present. In the presence of gramicidin, Ag+-induced Ca2+ efflux from intact ROS was blocked by 50 microM tetracaine or L-cis diltiazem, whereas without gramicidin both blockers were ineffective. Both L-cis diltiazem and tetracaine are blockers of one kinetic component of cGMP-induced Ca2+ flux across ROS disk membranes. The ion selectivity of the Ag+-induced pathway proved to be broad with little discrimination between the alkali cations Li+, Na+, K+, and Cs+ or between Ca2+ and Mg2+. The properties of the Ag+-induced pathway(s) suggest that it may reflect the cGMP-dependent conductance opened in the absence of cGMP by silver ions.
authors.affiliation: University of Calgary, Department of Medical Biochemistry, Alberta, Canada.
authors.forename: P P
authors.initials: PP
authors.lastname: Schnetkamp
authors.forename: R T
authors.initials: RT
authors.lastname: Szerencsei
mesh_terms: D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D002414:Cations, Monovalent / Q000493:pharmacokinetics*; D002417:Cattle; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D012834:Silver / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D002414:Cations, Monovalent; D013439:Sulfhydryl Reagents; D013748:Tetracaine; D012834:Silver; D004110:Diltiazem; D002118:Calcium