Effects of ginkgolide B on neuronal discharges in paraventricular nucleus of rat hypothalamic slices

Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.

La^(3+) Transmembrane Research in Guinea Pig Ventricular Cells by Fura-2 Fluorescence

Binding of La3+ to Fura-2 can change 340/380 nm fluorescence intensity ratio. Whether La3+ cross ventricular cell membrane was detected by this fluorescent probe technique. Fura-2 loaded isolated guinea pig ventricular cells were exposed to 0.01-0.1 mM extracellular Lanthanum ion concentration, 340nm/380 nm fluorescence ratio was not changed. Using calcium channel agonist BAY K8644, KCL (35mM) depolarization to open the voltage-dependent calcium channel (VDCC); Adrenoceptor agonist to excite adrenoceptor, 340/380 ratio was not changed, suggesting that La3+can not enter guinea pig ventricular cells in this case.

BEHAVIOR AND ACTIVITIES IN THE CENTRAL NERVOUS SYSTEM AFTER ACTIVATION OF L-TYPE CALCIUM CHANNELS IN MICE

The distribution of the immediate early gene c-fos expression in the mouse central nervous system after subcutaneous injection of Bay K 8644 was observed immunohistochemically. Half an hour after injection, cfos protein (FOS) was expressed in the piriform cortex, sensorimotor cortex, caudate putamen, thalamic paraventricular nucleus and striate cortex,etc. Intense FOS immunoreactive (FOS-ir) cells were seen during 2 ～ 4 h after injection. The restllts suggested that the distribution of FOS-ir ce1ls after subcutaneous injection of Bay K 8644 was coincldent with that of L-type calcium channels in the different areas of the CNS. After Bay K 8644 injection, mice appeared seizure-like behavior. The percentage of cells double-labelled by FOS and CaBP immunoreactivities in the observed regions was about 60. 2～72. 8% in CaBP-ir cells. It suggested that most CaBP-lr cells may have L-type calcium channels.

Hydrogen sulfide facilitates carotid sinus baroreceptor activity in anesthetized male rats

Background It has been reported that hydrogen sulfide （H2S） could relax vascular smooth muscle by direct activation of KATP channels and hyperpolarization of the membrane potential. Recently, our study has shown that H2S facilitated carotid baroreflex. This study was conducted to investigate the effect of H2S on carotid baroreceptor activity （CBA）. Methods The functional curve of carotid baroreceptor （FCCB） was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Results H2S （derived from NariS） 25, 50 and 100 pmol/L facilitated CBA, which shifted FCCB to the left and upward. There was a marked increase in peak slope （PS） and peak integral value of carotid sinus nerve charge （PIV） in a concentration-dependent manner. Pretreatment with glibenclamide （20 pmol/L）, a KATP channel blocker, the above effects of H2S on CBA were abolished. Pretreatment with Bay K8644 （an agonist of calcium channels, 500 nmol/L） eliminated the role of H2S on CBA. An inhibitor of cystathionine y-lyase （CSE）, DL-propargylglycine （PPG, 200 pmol/L） inhibited CBA in male rats and shifted FCCB to the right and downward. Conclusions Our results suggest that exogenous H2S exerts a facilitatory role on isolated CBA through opening KATP channels and further closing the calcium channels in vascular smooth muscle. Endogenous H2S may activate CBA in vivo.