期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 323, 期 1, 页码 356-364出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.107.126144
关键词
-
资金
- NIAAA NIH HHS [R01 AA014949, AA-14284, AA-007673, P60 AA011605-090005, R01 AA014949-04, R01 AA014284, AA-11605, P60 AA011605, R01 AA014284-04] Funding Source: Medline
Recent data have demonstrated that ethanol increases gamma-aminobutyric acid (GABA) release in many brain regions, but little is known about the mechanism responsible for this action. Consistent with previous results, ethanol increased miniature inhibitory postsynaptic current (mIPSC) frequency at the interneuron-Purkinje cell synapse in the slice and in mechanically dissociated neurons. These data suggest that ethanol is increasing spontaneous GABA release at this synapse. It is generally accepted that ethanol increases levels of intracellular calcium and that changes in intracellular calcium can alter neurotransmitter release. Therefore, we examined the contribution of calcium-dependent pathways to the effect of ethanol on spontaneous GABA release at the interneuron-Purkinje cell synapse. Ethanol continued to increase mIPSC frequency in a nominally calcium-free extracellular solution and in the presence of a voltage-dependent calcium channel inhibitor, cadmium chloride. These data suggest that influx of extracellular calcium does not play a critical role in the mechanism of ethanolenhanced spontaneous GABA release. However, a sarco/endoplasmic-reticulum calcium ATPase pump inhibitor (thapsigargin), an inositol 1,4,5-trisphosphate receptor antagonist (2-aminoethoxydiphenylborate) and a ryanodine receptor antagonist (ryanodine) significantly reduced the ability of ethanol to increase mIPSC frequency. In addition, ethanol was still able to increase mIPSC frequency in the presence of intracellular 1,2bis(2-aminophenoxy) ethane- N, N, N ', N '-tetraacetic acid (BAPTA) and a cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4iodophenyl)-1-( 2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3carboxamide (AM-251); thus, retrograde messengers are not involved in ethanol-enhanced spontaneous GABA release. Overall, these data suggest that calcium release from presynaptic internal stores plays a vital role in the mechanism of ethanol-enhanced spontaneous GABA release at the interneuron-Purkinje cell synapse.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据