Effects of 17 beta-estradiol on early afterdepolarizations and L-type Ca2+ currents induced by endothelin-1 in guinea pig papillary muscles and ventricular myocytes.
By use of standard microelectrodes and whole cell patch clamp, the effects of 17 beta-estradiol on early afterdepolarizations (EADs) and increase of L-type Ca2+ currents (L-Ica) induced by endothelin-1 (ET-1) were studied in guinea pig ventricular papillary muscles and myocytes. The results indicated that superfusion with ET-1 for 30 min resulted in a marked prolongation of the action potential duration (APD) and caused stable EADs leading to triggered activity occurring at the plateau of the action potentials in isolated guinea pig ventricular papillary muscles. With the addition of 17 beta-estradiol (30 mumol/l), APD was shortened and EADs were decreased. In the patch clamp study, ET-1 induced an increase of mean peak L-Ica from 534.46 +/- 46.23 to 1003.15 +/- 39.12 (pA) with the peak voltage-current curve shifting to the left. When 17 beta-estradiol (30 mumol/l) was added, the L-Ica was decreased by up to 33.32% (p < 0.01) with the peak voltage-current curve shifting to the right. In contrast to the steady-state inactivation curve, ET-1 shifted the steady-state activation curve in the depolarization direction. However, with the addition of 17 beta-estradiol, the deviation of the steady-state activation and inactivation curves caused by ET-1 was suppressed. In conclusion, 17 beta-estradiol appears to attenuate the prolongation of APD and reduce EADs induced by ET-1 in guinea pig papillary muscles by its inhibitory effect on L-Ica.
Liu
B
B
Heart Center, Beijing Red Cross Chaoyang Hospital, P.R. China.
Hu
D
D
Wang
J
J
Liu
X L
XL
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D019332:Endothelin-1 / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects*
D015220:Calcium Channels; D019332:Endothelin-1; D004958:Estradiol