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 B (0.1, 1, 10 micromol/L; n = 27) into the perfusate for 2 min, 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 micromol/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 micromol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1 micromol/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 micromol/L).


CONCLUSIONS
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 (K(DR)).
Lin
Yue
Y
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
Wang
Ru
R
Wang
Xin
X
He
Rui-Rong
RR
Wu
Yu-Ming
YM
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*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002120:Calcium Channel Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D046934:Ginkgolides / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology
D002120:Calcium Channel Agonists; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D026902:Potassium Channel Blockers; D018698:Glutamic Acid; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C045856:ginkgolide B