Electrophysiological effects of phytoestrogen genistein on pacemaker cells in sinoatrial nodes of rabbits.
Abstract
AIM: 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.
CONCLUSION: 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.
Keywords:
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.
CONCLUSION: 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.