Electrophysiological effects of phytoestrogen genistein on pacemaker cells in sinoatrial nodes of rabbits.
OBJECTIVE
To study the electrophysiological effects of genistein (GST) on pacemaker cells in sinoatrial (SA) nodes of rabbits.


METHODS
Parameters of action potential (AP) in SA node were recorded using intracellular microelectrode technique.


RESULTS
GST (10 - 150 micromol/L) not only decreased the amplitude of action potential (APA), maximal rate of depolarization (Vmax) [from (6.2 +/- 2.8) to (2.8 +/- 1.4) V/s, P < 0.01], velocity of diastolic (phase 4) depolarization (VDD) [from (55 +/- 14) to (38 +/- 8) mV/s, P < 0.01], and rate of pacemaker firing (RPF) [from (154 +/- 23) to (107 +/- 25) beat/min, P < 0.01], but also prolonged duration of 90 % repolarization of action potential (APD90) in a concentration-dependent manner. Both elevation of calcium concentration (5 mmol/L) in superfusate and application of L-type Ca2+ channel agonist Bay K8644 (0.5 micromol/L) reversed the inhibitory effects of GST on pacemaker cells, while pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), an NO synthase inhibitor, failed to block the electrophysiological effects of GST.


CONCLUSIONS
GST exerted a negative chronotropic action and induced a delayed repolarization of pacemaker cells in SA nodes of rabbits. These effects were likely due to reduction in calcium influx and potassium efflux, but had no association with NO release.
Ma
Tao
T
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Fan
Zhen-Zhong
ZZ
He
Rui-Rong
RR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D007529:Isoflavones; D008297:Male; D008839:Microelectrodes; D048789:Phytoestrogens; D028321:Plant Preparations; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D024661:Potassium Channels, Inwardly Rectifying; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019833:Genistein; D002118:Calcium