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Actions of the anti-oestrogen agent clomiphene on outward K+ currents in rat ventricular myocytes.
Clin Exp Pharmacol Physiol. 2004 Jan-Feb; 31(1-2):86-95.CE

Abstract

1. The effects of clomiphene (CLM) on cardiac outward K+ current components from rat isolated ventricular myocytes were investigated using the whole-cell patch-clamp technique. Clomiphene (10 micromol/L) significantly inhibited both peak (Ipeak) and end-pulse (Ilate) outward currents (elicited by a 500 msec voltage step from -40 to +50 mV in the presence of K+-containing intracellular and extracellular solutions) by approximately 37% (n = 6; P < 0.01) and 49% (n = 6; P < 0.01), respectively. In contrast, CLM had no effect on outward currents when K+-free solutions were used. 2. A double-pulse protocol and Boltzmann fitting were used to separate individual K+ current components on the basis of their voltage-dependent inactivation properties. At potentials positive to -80 mV, two inactivating transient outward components (Ito) and (IKx) and a non-inactivating steady state component (Iss) could be distinguished. 3. Clomiphene inhibited both Ito and Iss. The maximal block of Ito and Iss induced by CLM (100 micromol/L) was approximately 61% (n = 5) and 43% (n = 5) with IC50 values of 1.54 +/- 0.39 and 2.2 +/- 0.4 micromol/L, respectively. In contrast, the peak magnitude of IKx was unaltered by CLM, although its time-course of inactivation was accelerated. 4. Further experiments whereby myocytes were superfused with the vasoactive peptide endothelin (ET)-1 (20 nmol/L) revealed that CLM (10 micro mol/L) completely abolished the ET-1-sensitive component of Iss. 5. Our findings demonstrate, for the first time, the effects of CLM on distinct cardiac K+ current components and show that CLM modulates the voltage-gated K+ current components Ito and IKx and inhibits the steady state outward current Iss in rat ventricular myocytes.

Authors+Show Affiliations

Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14756690

Citation

Borg, John J., et al. "Actions of the Anti-oestrogen Agent Clomiphene On Outward K+ Currents in Rat Ventricular Myocytes." Clinical and Experimental Pharmacology & Physiology, vol. 31, no. 1-2, 2004, pp. 86-95.
Borg JJ, Hancox JC, Hogg DS, et al. Actions of the anti-oestrogen agent clomiphene on outward K+ currents in rat ventricular myocytes. Clin Exp Pharmacol Physiol. 2004;31(1-2):86-95.
Borg, J. J., Hancox, J. C., Hogg, D. S., James, A. F., & Kozlowski, R. Z. (2004). Actions of the anti-oestrogen agent clomiphene on outward K+ currents in rat ventricular myocytes. Clinical and Experimental Pharmacology & Physiology, 31(1-2), 86-95.
Borg JJ, et al. Actions of the Anti-oestrogen Agent Clomiphene On Outward K+ Currents in Rat Ventricular Myocytes. Clin Exp Pharmacol Physiol. 2004 Jan-Feb;31(1-2):86-95. PubMed PMID: 14756690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Actions of the anti-oestrogen agent clomiphene on outward K+ currents in rat ventricular myocytes. AU - Borg,John J, AU - Hancox,Jules C, AU - Hogg,Dayle S, AU - James,Andrew F, AU - Kozlowski,Roland Z, PY - 2004/2/6/pubmed PY - 2004/9/29/medline PY - 2004/2/6/entrez SP - 86 EP - 95 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 31 IS - 1-2 N2 - 1. The effects of clomiphene (CLM) on cardiac outward K+ current components from rat isolated ventricular myocytes were investigated using the whole-cell patch-clamp technique. Clomiphene (10 micromol/L) significantly inhibited both peak (Ipeak) and end-pulse (Ilate) outward currents (elicited by a 500 msec voltage step from -40 to +50 mV in the presence of K+-containing intracellular and extracellular solutions) by approximately 37% (n = 6; P < 0.01) and 49% (n = 6; P < 0.01), respectively. In contrast, CLM had no effect on outward currents when K+-free solutions were used. 2. A double-pulse protocol and Boltzmann fitting were used to separate individual K+ current components on the basis of their voltage-dependent inactivation properties. At potentials positive to -80 mV, two inactivating transient outward components (Ito) and (IKx) and a non-inactivating steady state component (Iss) could be distinguished. 3. Clomiphene inhibited both Ito and Iss. The maximal block of Ito and Iss induced by CLM (100 micromol/L) was approximately 61% (n = 5) and 43% (n = 5) with IC50 values of 1.54 +/- 0.39 and 2.2 +/- 0.4 micromol/L, respectively. In contrast, the peak magnitude of IKx was unaltered by CLM, although its time-course of inactivation was accelerated. 4. Further experiments whereby myocytes were superfused with the vasoactive peptide endothelin (ET)-1 (20 nmol/L) revealed that CLM (10 micro mol/L) completely abolished the ET-1-sensitive component of Iss. 5. Our findings demonstrate, for the first time, the effects of CLM on distinct cardiac K+ current components and show that CLM modulates the voltage-gated K+ current components Ito and IKx and inhibits the steady state outward current Iss in rat ventricular myocytes. SN - 0305-1870 UR - https://www.unboundmedicine.com/medline/citation/14756690/Actions_of_the_anti_oestrogen_agent_clomiphene_on_outward_K+_currents_in_rat_ventricular_myocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0305-1870&amp;date=2004&amp;volume=31&amp;issue=1-2&amp;spage=86 DB - PRIME DP - Unbound Medicine ER -