Vol. 303, Issue 1, 282-292, October 2002

Inhibitory Effects of the Antiestrogen Agent Clomiphene on Cardiac Sarcolemmal Anionic and Cationic Currents

John J. Borg, Kathryn H. Yuill¹ , Jules C. Hancox, Ian C. Spencer² and Roland Z. Kozlowski

Departments of Pharmacology (J.J.B., R.Z.K.) and Physiology and Cardiovascular Research Laboratories (K.H.Y., J.C.H.), School of Medical Sciences, University of Bristol, Bristol, United Kingdom

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,vol, activated by cell swelling after hypotonic shock (~145 mOsM)] with an IC₅₀ value of ~9.4 µM. In contrast, at concentrations up to 100 µM, clomiphene failed to inhibit both the chloride current activated by cyclic AMP (I_Cl,cAMP) and the anionic background current (I_AB). At 10 µM, clomiphene blocked the voltage-gated fast sodium current and the L-type calcium current (I_Ca,L) in both species. The voltage-independent fractional block of I_Ca,L induced by clomiphene (10 µM) was ~82%, this concentration also inhibited the inwardly rectifying K⁺ current with a fractional current block of ~26% at 90 mV. Fractional block of outward current at +70 mV in rat was ~25%, implying that delayed rectifying K⁺ channels were also affected by clomiphene. We conclude that clomiphene shows selectivity for I_Cl,vol over I_Cl,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.