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CARDIOVASCULAR

Effects of Phloretin and Phloridzin on Ca²⁺ Handling, the Action Potential, and Ion Currents in Rat Ventricular Myocytes

Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada (M.L.O., M.E.K., G.J.K.); and Department of Physiology, Queen's University, Kingston, Ontario, Canada (C.A.W.)

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 (I_to). 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 I_to. 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.

Address correspondence to: Dr. Gary J. Kargacin, Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada. E-mail kargacin{at}ucalgary.ca