Premium
Effect of 17β‐oestradiol on contraction, Ca 2+ current and intracellular free Ca 2+ in guinea‐pig isolated cardiac myocytes
Author(s) -
Jiang Canwen,
PooleWilson Philip A.,
Sarrel Philip M.,
Mochizuki Seibu,
Collins Peter,
MacLeod Kenneth T.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14403.x
Subject(s) - fura 2 , chemistry , endocrinology , medicine , intracellular , myocyte , contraction (grammar) , voltage clamp , isoprenaline , guinea pig , biophysics , membrane potential , biology , biochemistry , cytosol , stimulation , enzyme
1 The effect of 17β‐oestradiol on cardiac cell contraction, inward Ca 2+ current and intracellular free Ca 2+ ([free Ca 2+ ] 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 Ca 2+ ] i was measured with the Ca 2+ indicator, Fura‐2. 2 17β‐Oestradiol (10, 30 μ m ) caused a decrease in cell shortening at both 22 and 35°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. 17β‐Oestradiol (10, 30 μ m ) induced a similar decrease in cell shortening in voltage‐clamped and current‐clamped cells. 3 In Fura‐2 loaded cells, 17β‐oestradiol (10 and 30 μ m ) decreased systolic Fura‐2 fluorescence to 72 ± 7% and 47 ± 4% ( n = 6, P < 0.001) of control respectively. 17β‐Oestradiol (10 μ m ) had no significant effect on diastolic Fura‐2 fluorescence, but at higher concentration (30 μ m ) induced a slight decrease in resting Fura‐2 fluorescence. The effect of 17β‐oestradiol was reversible after 1–2 min of washout of the steroid. 4 17β‐Oestradiol (10 and 30 μ m ) decreased the peak inward Ca 2+ current ( I Ca ), which was sensitive to [Ca 2+ ] o , dihydropyridines and isoprenaline, to 59 ± 3% and 39 ± 5% ( n = 7∼9, P < 0.01) respectively, without producing any significant change in the shape of the current‐voltage relationship. 5 The recovery time of I Ca from inactivation was delayed by 17β‐oestradiol (10 μ m ). The inhibitory effect of 17β‐oestradiol on I Ca was less at a holding potential of −80 mV than at −40mV. 6 We conclude that 17β‐oestradiol has a negative inotropic effect on guinea‐pig single ventricular myocytes by inhibiting I Ca and so reducing systolic [Ca 2+ ] i . 17β‐Oestradiol may therefore have a Ca 2+ channel blocking property in guinea‐pig isolated ventricular myocytes.