Inhibitory effect of lead on GABA A receptor-mediated currents and GABAergic synaptic transmission in rat cortical neurons
10.3867/j.issn.1000-3002.2024.01.004
- VernacularTitle:铅对大鼠皮质神经元γ-氨基丁酸A型受体介导电流及GABA能突触传递的抑制作用
- Author:
Wenliang GAO
1
;
Hong ZHANG
;
Yi YUAN
;
Rui GUO
;
Xingyang LIU
;
Xianhua DENG
;
Hao SUN
Author Information
1. 济南市第二妇幼保健院,山东 济南 271100
- Keywords:
lead;
γ-aminobutyric acid A receptor;
cortical neurons;
spontaneous inhibitory post-synaptic currents;
miniature inhibitory post-synaptic currents
- From:
Chinese Journal of Pharmacology and Toxicology
2024;38(1):31-38
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.
