RT Journal Article
SR Electronic
T1 Inhibitory Effects of the Antiestrogen Agent Clomiphene on Cardiac Sarcolemmal Anionic and Cationic Currents
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 282
OP 292
DO 10.1124/jpet.102.038901
VO 303
IS 1
A1 John J. Borg
A1 Kathryn H. Yuill
A1 Jules C. Hancox
A1 Ian C. Spencer
A1 Roland Z. Kozlowski
YR 2002
UL http://jpet.aspetjournals.org/content/303/1/282.abstract
AB 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 [ICl,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 (ICl,cAMP) and the anionic background current (IAB). At 10 μM, clomiphene blocked the voltage-gated fast sodium current and the L-type calcium current (ICa,L) in both species. The voltage-independent fractional block ofICa,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 ICl,vol overICl,cAMP and IABand 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. The American Society for Pharmacology and Experimental Therapeutics