Effect of 17 beta-oestradiol on contraction, Ca2+ current and intracellular free Ca2+ in guinea-pig isolated cardiac myocytes.
1. The effect of 17 beta-oestradiol on cardiac cell contraction, inward Ca2+ current and intracellular free Ca2+ ([free Ca2+]i) was investigated in guinea-pig single, isolated ventricular myocytes. The changes of cell length were measured by use of a photodiode array, the voltage-clamp experiments were performed with a switch clamp system and [free Ca2+]i was measured with the Ca2+ indicator, Fura-2. 2. 17 beta-Oestradiol (10, 30 microM) caused a decrease in cell shortening at both 22 and 35 degrees C. This negative inotropic effect was accompanied by a decrease in action potential duration mainly brought about by a shortening of the plateau region of the action potential. 17 beta-Oestradiol (10, 30 microM) induced a similar decrease in cell shortening in voltage-clamped and current-clamped cells. 3. In Fura-2 loaded cells, 17 beta-oestradiol (10 and 30 microM) decreased systolic Fura-2 fluorescence to 72 +/- 7% and 47 +/- 4% (n = 6, P less than 0.001) of control respectively. 17 beta-Oestradiol (10 microM) had no significant effect on diastolic Fura-2 fluorescence, but at higher concentration (30 microM) induced a slight decrease in resting Fura-2 fluorescence. The effect of 17 beta-oestradiol was reversible after 1-2 min of washout of the steroid. 4. 17 beta-Oestradiol (10 and 30 microM) decreased the peak inward Ca2+ current (ICa), which was sensitive to [Ca2+]o, dihydropyridines and isoprenaline, to 59 +/- 3% and 39 +/- 5% (n = 7 approximately 9, P less than 0.01) respectively, without producing any significant change in the shape of the current-voltage relationship.5. The recovery time of ICa from inactivation was delayed by 17beta-oestradiol (10microM). The inhibitory effect of 17beta-oestradiol on ICa was less at a holding potential of -80 mV than at -40 mV.6. We conclude that 17beta-oestradiol has a negative inotropic effect on guinea-pig single ventricular myocytes by inhibiting ICa and so reducing systolic [Ca2+]i. 17beta-Oestradiol may therefore have a Ca2+ channel blocking property in guinea-pig isolated ventricular myocytes.
Jiang
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Department of Cardiac Medicine, National Heart and Lung Institute, London.
Poole-Wilson
P A
PA
Sarrel
P M
PM
Mochizuki
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S
Collins
P
P
MacLeod
K T
KT
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D016257:Fura-2; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology
D004958:Estradiol; D002118:Calcium; D016257:Fura-2