Electrophysiologic effects of 17β-estradiol on pacemaker cells in sinoatrial nodes of rabbits / 生理学报

To investigate the electrophysiological effects of 17β-estradiol on pacemaker cells in sinoatrial (SA) nodes of rabbits and the underlying mechanism, intracellular microelectrode technique was used to record action potential (AP) in SA node cells of rabbits. The results showed that: (1) 17β-estradiol (1, 10, 100 μmol/L) not only significantly decreased the amplitude of action potential (APA) and the maximal rate of depolarization (V(max)), but also decreased the velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF) in a concentration-dependent manner. The AP duration at 50% repolarization (APD(50)) and at 90% repolarization (APD(90)) were prolonged. But the maximal diastolic potential (MDP) was not affected. (2) Pretreatment with tamoxifen (10 μmol/L), an inhibitor of estrogen receptor, did not block the electrophysiological effects of 17β-estradiol (10 μmol/L) on SA node cells. (3) Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L), a nitric oxide (NO) synthase inhibitor, completely abolished the electrophysiological effects of 17β-estradiol (10 μmol/L) on SA node cells. The results suggest that 17β-estradiol inhibits the electrophysiological activity of pacemaker cells in SA nodes of rabbits in a concentration-dependent manner possibly through a non-genomic mechanism related with NO.

Resveratrol inhibits neuronal discharges in rat hippocampal CA1 area / 生理学报

The effects of resveratrol on the discharges of neurons in CA1 area of rat hippocampal slices were examined by using extracellular recording technique. The results are as follows: (1) In response to the application of resveratrol (0.05, 0.5, 5.0 micromol/L, n=52) into the superfusate for 2 min, the spontaneous discharge rate of 46/52 (88.5%) neurons was significantly decreased in a dose-dependent manner; (2) Application of L-glutamate (0.2 mmol/L) into the superfusate led to a marked increase in discharge rate of all 8 (100%) slices in an epileptiform pattern. The increased discharges were suppressed by application of resveratrol (5.0 micromol/L); (3) In 7 slices, perfusion of the selective L-type calcium channel agonist, Bay K8644 (0.1 micromol/L), induced a significant increase in the discharge rate of 6/7 (85.7%) slices. The increased discharges were suppressed by application of resveratrol (5.0 micromol/L); (4) In 9 slices, perfusion of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 micromol/L) into the superfusate significantly augmented the discharge rate of 7/9 (77.8%) slices. Resveratrol (5.0 micromol/L) applied into the superfusate reduced the increased discharges of all 7/7 (100%) neurons; (5) In 10 units, the large-conductance Ca(2+)-activated K(+) channel blocker (tetraethylammonium chloride, TEA, 1 mmol/L) significantly increased the discharge rate of 9/10 (90%) slices. Resveratrol (5.0 micromol/L) applied into the superfusate inhibited the discharges of 8/9 (88.9%) slices. These results suggest that resveratrol inhibits the electrical activity of CA1 neurons. This effect may be related to the blockade of L-type calcium channel and a subsequent reduction of calcium influx, and probably has no association with large-conductance Ca(2+)-activated K(+) channel.

Resveratrol inhibits the electrical activity of subfornical organ neurons in rat / 生理学报

The effects of resveratrol on the discharges of neurons in rat subfornical organ (SFO) slices were examined by using extracellular recording technique. The results are as follows: (1) In response to the application of resveratrol (1, 5, 10 mumol/L, n=65) into the superfusate for 2 min, the spontaneous discharge rate of 60/65 (92.3%) neurons was significantly decreased in a dose-dependent manner;(2) Application of L-glutamate (0.3 mmol/L) into the superfusate led to a marked increase in discharge rate of all 12 (100%) neurons in an epileptiform pattern. The increased discharges of 10/12 (83.3%) neurons were suppressed by application of resveratrol (5 mumol/L);(3) In 8 neurons, the selective L-type calcium channel agonist, Bay K8644 (0.1 mumol/L), induced a significant increase in discharge rate of all 8 (100%) neurons. The increased discharges of all 8 (100%) neurons were suppressed by resveratrol (5 mumol/L);(4) In 14 neurons, nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) 50 mumol/L significantly increased the discharge rate of 11/14 (78.6%) neurons. Resveratrol (5 ?mol/L) applied into the superfusate reduced the increased discharges of 9/11 (81.8%) neurons;(5) In 12 neurons, the large-conductance Ca(2+)-activated K(+) channel blocker tetraethylammonium chloride (TEA) 1 mmol/L significantly increased the discharge rate of 10/12 (83.3%) neurons. Resveratrol (5 mumol/L) inhibited the increased discharges of 9/10 (90%) neurons. These results suggest that resveratrol inhibits the electrical activity of SFO neurons. This effect may be related to its properties of blockade of L-type voltage-gated calcium channel and nitric oxide (NO) promoting, and probably has no association with large-conductance Ca(2+)-activated K(+) channel.

High-frequency electrical stimulation of femoral nerve reduces infarct size following myocardial ischemia-reperfusion in rats / 生理学报

The effects of femoral nerve electrostimulation (FNES) on ischemia-reperfused myocardium were examined in the urethane- anesthetized rats to determine whether FNES may provide cardioprotection and to observe the possible mechanism. The area at risk (AR) and infarct area (IA) were determined using Evans blue and nitro-blue tetrazolium staining, respectively. Infarct size (IS) was defined as 100xIA/AR (%). The results are as follows: (1) During 30 min myocardial ischemia and subsequent 120 min reperfusion, the myocardial infarct size occupied (54.96+/-0.82)% of the area at risk. (2) FNES of high frequency (10 V, 100 Hz, 1 ms) significantly reduced myocardial infarct size to (36.94+/-1.34)% (P<0.01), indicating the cardioprotective effect FNES of high frequency on myocardial ischemia-reperfusion, while FNES of low frequency (10 V, 10 Hz, 1 ms) had no effect on myocardial infarct size. (3) Pretreatment with either naloxone (5 mg /kg, i.v), a nonselective opioid receptor antagonist, or glibenclamide (5 mg /kg, i.v), a K(ATP) channel antagonist, completely abolished the cardioprotection of FNES (100 Hz) from myocardial ischemia-reperfusion. It is suggested that FNES of high frequency can protect myocardium from ischemia-reperfusion injury. The possible mechanism is that FNES of high frequency may induce the release of opioids from the central nervous system, and the activation of opioid receptors in the heart results in an opening of myocardial K(ATP) channels which can protect myocardium.