Inhibitory effects of the antiestrogen agent clomiphene on cardiac sarcolemmal anionic and cationic currents

The aim of this study was to determine the effects of the antiestrogen agent clomiphene on cardiac anionic and cationic sarcolemmal ion channels. Whole-cell recordings were made from rat and guinea pig ventricular myocytes. Clomiphene inhibited the volume-regulated chloride current [I-Cl,I-vol, activated by cell swelling after hypotonic shock (similar to145 mOsM)] with an IC50 value of similar to9.4 muM. In contrast, at concentrations up to 100 muM, clomiphene failed to inhibit both the chloride current activated by cyclic AMP (I-Cl,I- cAMP) and the anionic background current (I-AB). At 10 muM, clomiphene blocked the voltage-gated fast sodium current and the L-type calcium current (I-Ca,I- L) in both species. The voltage-independent fractional block of I-Ca,I- L induced by clomiphene (10 muM) was similar to82%, this concentration also inhibited the inwardly rectifying K+ current with a fractional current block of similar to26% at -90 mV. Fractional block of outward current at +70 mV in rat was similar to25%, implying that delayed rectifying K+ channels were also affected by clomiphene. We conclude that clomiphene shows selectivity for I-Cl,I-vol over I-Cl,I- cAMP and I-AB and therefore represents a useful tool for studying chloride conductances in isolated ventricular myocytes with interfering currents blocked. However, due to its effects on cation conductances it would be of little value in this regard for other types of in vitro or in vivo experiments.