title: Gadolinium inhibits Na(+)-Ca(2+) exchanger current in guinea-pig isolated ventricular myocytes.
abstract: The trivalent cation, gadolinium (Gd(3+)) is commonly used to inhibit stretch-activated channels. In this report, we show that Gd(3+) also inhibits ionic current (I(NaCa)), carried by the Na(+)-Ca(2+) exchanger protein. Under selective recording conditions, Gd(3+) inhibited both outward and inward I(NaCa) from guinea-pig isolated ventricular myocytes in a dose-dependent manner, with half-maximal inhibition concentrations (IC(50)) of 30.0+/-4.0 microM at +60 mV (Hill-coefficient, h=1.04+/-0.13) and 20.0+/-2.7 microM at -100 mV (h=1.13+/-0.16), respectively (P>0.05, n=5 - 9). Thus, inhibition was not voltage-dependent. The time from Gd(3+) application to steady-state effect was slow compared to the divalent blocker Ni(2+). The slow time course appeared to reflect gradual Gd(3+) accumulation at its binding site on the exchanger, rather than a use-dependent blocking mechanism. This study indicates that for experiments in which Gd(3+) is used, its inhibitory effect on I(NaCa) should be taken into account.
authors.affiliation: Department of Physiology & Cardiovascular Research Laboratories, School of Medical Sciences, Bristol University, University Walk, Bristol, BS8 1TD.
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: J C
authors.initials: JC
authors.lastname: Hancox
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*
chemical_list: D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D009532:Nickel; D005682:Gadolinium