Gadolinium inhibits Na + ‐Ca 2+ exchanger current in guinea‐pig isolated ventricular myocytes

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 μ M at +60 mV (Hill‐coefficient, h=1.04±0.13) and 20.0±2.7 μ M 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. British Journal of Pharmacology (2000) 130 , 485–488; doi: 10.1038/sj.bjp.0703353