[1-9]The Yin and Yang of GABAA signaling

报告题目：The Yin and Yang of GABAA signaling

报 告 人：Yi Zhu, Ph.D.（University of Pittsburgh）

报告时间：2014年1月9日（周四） 下午14:00

报告地点：独墅湖校区二期云轩楼2301室

Biography

Yi Zhu received a B.S. in Pharmacology from China Pharmaceutical University. She then joined the department of pharmacology in Soochow University and got a M.S. in Pharmacology here. Dr. Zhu obtained her Ph.D. in Neuroscience Programme from The University of Maryland in the laboratory of Dr. Michael Gold. Her thesis project focused on the change of periphery GABAA signaling following chronic inflammation. After her graduation in 2011, Dr. Zhu was recruited as a postdoctoral fellow by Professor Steve A. Prescott at The University of Pitts burgh, center for pain research, where she combined computational modeling and dynamic clamp to study the excitability of dorsal root ganglion neurons and the effect of GABA. Dr. Zhu is currently an postdoctoral Associate in Professor Gerald Gebhart's laboratory at the center for pain research in University of Pittsburgh where she conducts research using channelrhodpsin mice to study the excitability and action potential conduction in the peripheral terminals of colon sensory fibers. 

Abstract

Persistent inflammation is associated with a shift in spinal GABA(A) signaling from inhibition to excitation such that GABA(A)-receptor activation contributes to inflammatory hyperalgesia. We tested the hypothesis that the primary afferent is the site of the persistent inflammation-induced shift in GABA(A) signaling which is due to a Na(+)-K(+)-Cl(-)-co-transporter (NKCC1)-dependent depolarization of the GABA(A) current equilibrium potential (E(GABA)). Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion (DRG) neurons from naïve and inflamed (3 days after a subcutaneous injection of complete Freund's adjuvant) adult male rats were studied with Ca(2+) imaging, western blot and gramicidin-perforated patch recording. GABA evoked a Ca(2+) transient in a subpopulation of small- to medium-diameter capsaicin-sensitive cutaneous neurons. Inflammation was associated with a significant increase in the magnitude of GABA-induced depolarization as well as the percentage of neurons in which GABA evoked a Ca(2+) transient. There was no detectable change in NKCC1 protein or phosphoprotein at the whole ganglia level. Furthermore, the increase in excitatory response was comparable in both HEPES- and HCO(3)(-)-buffered solutions, but was only associated with a depolarization of E(GABA) in HCO(3)(-)-based solution. In contrast, under both recording conditions, the excitatory response was associated with an increase in GABA(A) current density, a decrease in low threshold K(+) current density, and resting membrane potential depolarization. Our results suggest that increasing K(+) conductance in afferents innervating a site of persistent inflammation may have greater efficacy in the inhibition of inflammatory hyperalgesia than attempting to drive a hyperpolarizing shift in E(GABA).