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Blockade of presynaptic 4-aminopyridine-sensitive potassium channels increases initial neurotransmitter release probability, reinstates synaptic transmission altered by GABAB receptor activation in rat midbrain periaqueductal gray

Li, Guangyinga,d,*; Liu, Zhi-Liangb,c,*; Zhang, Wei-Ningc; Yang, Kunc,d

doi: 10.1097/WNR.0000000000000499

The activation of γ-aminobutyric acid receptor subtype B (GABAB) receptors in the midbrain ventrolateral periaqueductal gray (vlPAG) induces both postsynaptic and presynaptic inhibition. Whereas the postsynaptic inhibition is mediated by G protein-coupled inwardly rectifying K+ channels, the presynaptic inhibition of neurotransmitter release is primarily mediated by voltage-gated calcium channels. Using whole-cell recordings from acute rat PAG slices, we report here that the bath application of 4-aminopyridine, a voltage-gated K+ channel blocker, increases the initial GABA and glutamate release probability (P) and reinstates P depressed by presynaptic GABAB receptor activation at inhibitory and excitatory synapses, respectively. However, Ba2+, which blocks G protein-coupled inwardly rectifying K+ channels, does not produce similar effects. Our data suggest that the blockade of presynaptic 4-aminopyridine-sensitive K+ channels in vlPAG facilitates neurotransmitter release and reinstates synaptic transmission that has been altered by presynaptic GABAB receptor activation. Because vlPAG is involved in the descending pain control system, the present results may have potential therapeutic applications.

aDepartment of Psychology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin

bBayi Brain Hospital, The Military General Hospital of Beijing PLA, Beijing

cDepartment of Basic Medical Sciences, School of Medicine

dAffiliated Hospital Electrophysiology Laboratory, Jiangsu University, Zhenjiang, Jiangsu, China

* Guangying Li, Zhi-Liang Liu contributed equally to the article.

Correspondence to Kun Yang, MD, PhD, Department of Basic Medical Sciences, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China Tel: +86 511 8595 9086; fax: +86 511 8503 8483; e-mail:

Received September 15, 2015

Accepted October 21, 2015

© 2016 Wolters Kluwer Health | Lippincott Williams & Wilkins