Gender determines the acute actions of genistein on intracellular calcium regulation in the guinea-pig heart.
OBJECTIVE
The soy-isoflavone, genistein, appears to be cardioprotective partly through direct actions on the heart, although the relative benefits between men and women are not fully known. The purpose of the present study was to determine whether gender influences the acute electrophysiological actions of genistein at the level of isolated cardiac myocytes and to elucidate the mechanisms involved.


METHODS
Left ventricular myocytes, isolated from weight-matched male and female guinea-pigs and rats, were field stimulated at a rate of 1 Hz in a superfusion chamber (37 degrees C). The effects of acute application of genistein on cell shortening and the Ca(2+) transients were measured. Electrophysiological recordings were performed using single electrode voltage-clamp.


RESULTS
Genistein increased cell contraction and the Ca(2+) transients in a concentration-dependent manner in myocytes from male guinea-pigs [by 54+/-11% and 22+/-4%, respectively (mean+/-S.E.M., p<0.001, n=18) at 40 microM], while having no significant corresponding effect in those from females. In contrast, genistein increased both parameters in myocytes obtained from male and female rats. The changes in guinea-pigs occurred despite inhibition of the L-type Ca(2+) current in both sexes (n>23, p<0.001). In order to explain these observations, we measured sarcoplasmic reticulum (SR) Ca(2+) contents by integrating the Na(+)/Ca(2+) exchanger currents (I(NCX)) following rapid caffeine application. Genistein increased I(NCX) integrals by 27% in males (n=12, p<0.01) and 20% in females (n=14, p<0.01). The increased SR Ca(2+) load in males, but not females, could be related to an impaired ability of the Na(+)/Ca(2+) exchanger to extrude Ca(2+).


CONCLUSIONS
We have demonstrated novel, gender-related differences in the acute cardiac actions of genistein, which can be attributed to actions at distinct points of the intracellular Ca(2+) cycle. Our results suggest that genistein may afford greater cardioprotection in females than in males.
Liew
Reginald
R
Cardiac Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, United Kingdom. r.liew@imperial.ac.uk
Stagg
Mark A
MA
Chan
Joachim
J
Collins
Peter
P
MacLeod
Kenneth T
KT
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D005260:Female; D005783:Gender Identity; D019833:Genistein / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
D015220:Calcium Channels; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium