title: Enhancement of an outwardly rectifying chloride channel in hippocampal pyramidal neurons after cerebral ischemia.
abstract: Cerebral ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms remain unclear, but it is known that apoptosis is involved in this process. Chloride efflux has been implicated in the progression of apoptosis in various cell types. Using both the inside-out and whole-cell configurations of the patch-clamp technique, the present study characterized an outwardly rectifying chloride channel (ORCC) in acutely dissociated pyramid neurons in the hippocampus of adult rats. The channel had a nonlinear current-voltage relationship with a conductance of 42.26±1.2pS in the positive voltage range and 18.23±0.96pS in the negative voltage range, indicating an outward rectification pattern. The channel is Cl(-) selective, and the open probability is voltage-dependent. It can be blocked by the classical Cl(-) channel blockers DIDS, SITS, NPPB and glibenclamide. We examined the different changes in ORCC activity in CA1 and CA3 pyramidal neurons at 6, 24 and 48h after transient forebrain ischemia. In the vulnerable CA1 neurons, ORCC activity was persistently enhanced after ischemic insult, whereas in the invulnerable CA3 neurons, no significant changes occurred. Further analysis of channel kinetics suggested that multiple openings are a major contributor to the increase in channel activity after ischemia. Pharmacological blockade of the ORCC partly attenuated cell death in the hippocampal neurons. We propose that the enhanced activity of ORCC might contribute to selective neuronal damage in the CA1 region after cerebral ischemia, and that ORCC may be a therapeutic target against ischemia-induced cell death.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: lijg71@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Quanzhong
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiawen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Jiantian
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Neurobiology, Southern Medical University, Guangzhou 510515, China. Electronic address: tgao@smu.edu.cn.
authors.forename: Tianming
authors.initials: T
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000503:physiopathology*; D002470:Cell Survival; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D055724:Electrophysiological Phenomena; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018118:Chloride Channels
keywords: Cell death; Cerebral ischemia; Chloride channel; Hippocampal neurons