EFFECT OF 17-BETA-ESTRADIOL ON CONTRACTION, CA-2+ CURRENT AND INTRACELLULAR FREE CA-2+ IN GUINEA-PIG ISOLATED CARDIAC MYOCYTES

EFFECT OF 17-BETA-ESTRADIOL ON CONTRACTION, CA-2+ CURRENT AND INTRACELLULAR FREE CA-2+ IN GUINEA-PIG ISOLATED CARDIAC MYOCYTES
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DOI:
10.1111/j.1476-5381.1992.tb14403.x
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发表时间:
1992-07-01
影响因子:
7.3
通讯作者:
MACLEOD, KT
MACLEOD, KT
中科院分区:
医学2区
文献类型:
--
作者:
JIANG, C;POOLEWILSON, PA;MACLEOD, KT

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1研究了17- β -雌二醇对心肌细胞收缩、向内Ca2+电流和细胞内游离Ca2+([游离Ca2+]i)的影响。使用光电二极管阵列测量细胞长度的变化,使用开关钳系统进行电压钳实验,使用Ca2+指示剂测量[游离Ca2+]i, Fura-2.2 17- β - oestradiol (10, 30 mu- m)在22和35℃下均导致细胞缩短减少。这种负性肌力效应伴随着动作电位持续时间的缩短,这主要是由于动作电位平台区缩短所致。17- β -雌二醇(10,30 μ mu- m)在电压箝位和电流箝位的细胞中诱导了类似的细胞缩短减少在携带Fura-2的细胞中,17- β -雌二醇(10 μ m和30 μ m)分别使对照组的收缩Fura-2荧光降低至72 +/- 7%和47 +/- 4% (n = 6, P < 0.001)。17- β -雌二醇(10 μ m)对舒张期Fura-2荧光无显著影响,但较高浓度(30 μ m)可引起静息期Fura-2荧光略有下降。17- β -雌二醇的作用在类固醇洗脱1 -2分钟后是可逆的。4 17- β -雌二醇(10和30 μ mu- m)使对[Ca2+]o、二氢吡啶和异丙肾上腺素敏感的Ca2+内向电流(I(Ca))的峰值分别降至59 +/- 3%和39 +/- 5% (n = 7约9,P < 0.01),但对电流-电压关系的形状没有产生显著变化17- β -雌二醇(10 μ m)可延迟I(Ca)从失活中恢复的时间。17- β -雌二醇对I(Ca)的抑制作用在-80 mV电位下比在-40 mV电位下更弱我们得出结论,17- β -雌二醇通过抑制I(Ca)从而降低收缩[Ca2+] I对豚鼠单心室肌细胞具有负性肌力作用。因此,17- β -雌二醇可能在豚鼠分离心室肌细胞中具有Ca2+通道阻断特性。
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-mu-M) 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-mu-M) 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-mu-M) decreased systolic Fura-2 fluorescence to 72 +/- 7% and 47 +/- 4% (n = 6, P < 0.001) of control respectively. 17-beta-Oestradiol (10-mu-M) had no significant effect on diastolic Fura-2 fluorescence, but at higher concentration (30-mu-M) 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-mu-M) decreased the peak inward Ca2+ current (I(Ca)), which was sensitive to [Ca2+]o, dihydropyridines and isoprenaline, to 59 +/- 3% and 39 +/- 5% (n = 7 approximately 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 17-beta-oestradiol (10-mu-M). The inhibitory effect of 17-beta-oestradiol on I(Ca) was less at a holding potential of -80 mV than at -40 mV.6 We conclude that 17-beta-oestradiol has a negative inotropic effect on guinea-pig single ventricular myocytes by inhibiting I(Ca) and so reducing systolic [Ca2+]i. 17-beta-Oestradiol may therefore have a Ca2+ channel blocking property in guinea-pig isolated ventricular myocytes.