RT Journal Article
SR Electronic
T1 EPAC Inhibition of SUR1 Receptor Increases Glutamate Release and Seizure Vulnerability
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8861
OP 8865
DO 10.1523/JNEUROSCI.5686-12.2013
VO 33
IS 20
A1 Zhao, Kunpeng
A1 Wen, Ruojian
A1 Wang, Xiaoxi
A1 Pei, Lei
A1 Yang, Ying
A1 Shang, You
A1 Bazan, Nicolas
A1 Zhu, Ling-Qiang
A1 Tian, Qing
A1 Lu, Youming
YR 2013
UL http://www.jneurosci.org/content/33/20/8861.abstract
AB EPAC (Exchange Proteins Activated by cAMP) regulates glutamate transmitter release in the central neurons, but a role underlying this regulation has yet to be identified. Here we show that EPAC binds directly to the intracellular loop of an ATP-sensitive potassium (KATP) channel type-1 sulfonylurea receptor (SUR1) receptor consisting of amino acids 859–881 (SUR1859–881). Ablation of EPAC or expression of SUR1859–881, which intercepts EPAC-SUR1 binding, increases the open probability of KATP channels consisting of the Kir6.1 subunit and SUR1. Opening of KATP channels inhibits glutamate release and reduces seizure vulnerability in adult mice. Therefore, EPAC interaction with SUR1 controls seizure susceptibility and possibly acts via regulation of glutamate release.