Lovinger D M, Harrison N L, Lambert N A
Section of Electrophysiology, LPPS, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Eur J Pharmacol. 1992 Feb 18;211(3):337-41. doi: 10.1016/0014-2999(92)90390-p.
The actions of 3-aminopropanephosphinic acid (APPA) were examined using whole-cell patch-clamp recording in rat hippocampal slice. In recordings from neurons in subfield CA1 of slices from young (2-4 weeks) and adult (greater than 2 month) rats, APPA (0.5-50 microM) produced membrane hyperpolarization and outward current under voltage-clamp. APPA also inhibited excitatory postsynaptic potentials with an IC50 of 2.3 microM, and reduced inhibitory postsynaptic potentials at concentrations from 0.1 to 1 microM. The hyperpolarizing and synaptic depressant effects of APPA were reduced by 2-OH-saclofen an antagonist at the B-type receptor for the neurotransmitter gamma-aminobutyric acid (GABA). In this preparation APPA exhibited potencies similar to those previously reported for the GABAB receptor agonist baclofen. APPA was much less effective in inhibiting synaptic transmission measured using field potential recordings. The observations made with whole-cell patch-clamp recording indicate that in hippocampus APPA acts as a potent agonist at presynaptic GABAB receptors associated with both excitatory and inhibitory synapses, and also activates postsynaptic GABAB receptors.
使用全细胞膜片钳记录技术在大鼠海马切片中研究了3-氨基丙基膦酸（APPA）的作用。在来自幼年（2-4周）和成年（大于2个月）大鼠切片CA1亚区神经元的记录中，APPA（0.5-50微摩尔）在电压钳制下产生膜超极化和外向电流。APPA还抑制兴奋性突触后电位，IC50为2.3微摩尔，并在0.1至1微摩尔浓度下降低抑制性突触后电位。APPA的超极化和突触抑制作用被2-羟基-舒氯芬减弱，2-羟基-舒氯芬是神经递质γ-氨基丁酸（GABA）B型受体的拮抗剂。在此制备中，APPA表现出与先前报道的GABAB受体激动剂巴氯芬相似的效力。APPA在使用场电位记录测量抑制突触传递方面效果要差得多。全细胞膜片钳记录的观察结果表明，在海马中，APPA作为一种强效激动剂作用于与兴奋性和抑制性突触相关的突触前GABAB受体，并且还激活突触后GABAB受体。
