Author:
Khatri Shailesh N.,Wu Wan-Chen,Yang Ying,Pugh Jason R.
Abstract
AbstractMany neurons, including cerebellar granule cells, exhibit a tonic GABA current mediated by extrasynaptic GABAAreceptors. This current is a critical regulator of firing and the target of many clinically relevant compounds. Using a combination of patch clamp electrophysiology and photolytic uncaging of RuBi-GABA we show that GABABreceptors are tonically active and enhance extrasynaptic GABAAreceptor currents in cerebellar granule cells. This enhancement is not associated with meaningful changes in GABAAreceptor potency, mean channel open-time, open probability, or single-channel current. However, there was a significant (~40%) decrease in the number of channels participating in the GABA uncaging current and an increase in receptor desensitization. Furthermore, we find that adenylate cyclase, PKA, CaMKII, and release of Ca2+from intracellular stores are necessary for modulation of GABAAreceptors. Overall, this work reveals crosstalk between postsynaptic GABAAand GABABreceptors and identifies the signaling pathways and mechanisms involved.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
Publisher
Springer Science and Business Media LLC
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献