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

Abstract

The trivalent cation, gadolinium (Gd3+) is commonly used to inhibit stretch-activated channels. In this report, we show that Gd3+ also inhibits ionic current (I(NaCa)), carried by the Na+-Ca2+ exchanger protein. Under selective recording conditions, Gd3+ inhibited both outward and inward I(NaCa) from guinea-pig isolated ventricular myocytes in a dose-dependent manner, with half-maximal inhibition concentrations (IC50) of 30.0 ± 4.0 μM at +60 mV (Hill-coefficient, h = 1.04 ± 0.13) and 20.0 ± 2.7 μM at -100 mV (h = 1.13 ± 0.16), respectively (P > 0.05, n = 5-9). Thus, inhibition was not voltage-dependent. The time from Gd3+ application to steady-state effect was slow compared to the divalent blocker Ni2+. The slow time course appeared to reflect gradual Gd3+ accumulation at its binding site on the exchanger, rather than a use-dependent blocking mechanism. This study indicates that for experiments in which Gd3+ is used, its inhibitory effect on I(NaCa) should be taken into account.