Abstract
The effects of the phytoestrogens phloretin and phloridzin on Ca2+ handling, cell shortening, the action potential, and Ca2+ and K+ currents in freshly isolated cardiac myocytes from rat ventricle were examined. Phloretin increased the amplitude and area and decreased the rate of decline of electrically evoked Ca2+ transients in the myocytes. These effects were accompanied by an increase in the Ca2+ load of the sarcoplasmic reticulum, as determined by the area of caffeine-evoked Ca2+ transients. An increase in the extent of shortening of the myocytes in response to electrically evoked action potentials was also observed in the presence of phloretin. To further examine possible mechanisms contributing to the observed changes in Ca2+ handling and contractility, the effects of phloretin on the cardiac action potential and plasma membrane Ca2+ and K+ currents were examined. Phloretin markedly increased the action potential duration in the myocytes, and it inhibited the Ca2+-independent transient outward K+ current (Ito). The inwardly rectifying K+ current, the sustained outward delayed rectifier K+ current, and L-type Ca2+ currents were not significantly different in the presence and absence of phloretin, nor was there any evidence that the Na+/Ca2+ exchanger was affected. The effects of phloretin on Ca2+ handling in the myocytes are consistent with its effects on Ito. Phloridzin did not significantly alter the amplitude or area of electrically evoked Ca2+ transients in the myocytes, nor did it have detectable effects on the sarcoplasmic reticulum Ca2+ load, cell shortening, or the action potential.
Footnotes
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This work was supported by the Heart and Stroke Foundation of Alberta, Heart and Stroke Foundation of Ontario Grant T5234, and the Canadian Institutes of Health Research. M.L.O. was supported by a studentship from the Heart and Stroke Foundation of Canada and by a travel award from the University of Calgary.
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C.A.W. and G.J.K. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.121111.
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ABBREVIATIONS: SR, sarcoplasmic reticulum; SERCA, sarco(endo)plasmic reticulum Ca2+ ATPase; BSA, bovine serum albumin; AM, acetoxymethyl ester; Ito, Ca2+-independent transient outward K+ current; Isus, sustained outward delayed rectifier K+ current; IK1, inwardly rectifying K+ current, ICa,L, L-type Ca2+ current.
- Received February 8, 2007.
- Accepted March 20, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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