Gadolinium inhibits Na+ -Ca2+ exchanger current in guinea-pig isolated ventricular myocytes

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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.