Activation of calcium-dependent potassium channels in rat brain neurons by neurotrophin-3 and nerve growth factor

被引:63
作者
Holm, NR
Christophersen, P
Olesen, SP
Gammeltoft, S
机构
[1] UNIV COPENHAGEN,SCH MED,GLOSTRUP HOSP,DEPT CLIN BIOCHEM,DK-2600 GLOSTRUP,DENMARK
[2] NEUROSEARCH,DK-2600 GLOSTRUP,DENMARK
关键词
D O I
10.1073/pnas.94.3.1002
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The neurotrophins are signaling factors that are essential for survival and differentiation of distinct neuronal populations during the development and regeneration of the nervous system. The long-term effects of neurotrophins have been studied in detail, but little is known about their acute effects on neuronal activity. Here we use permeabilized whole-cell patch clamp to demonstrate that neurotrophin-3 (NT-3) and nerve growth factor activate calcium-dependent, paxilline-sensitive potassium channels (BK channels) in cortical neurons. Application of NT-3 or nerve growth factor produced a rapid and gradual rise in BK current that was sustained for 30-50 min; brain-derived neurotrophic factor, ciliary neurotrophic factor, and insulin-like growth factor-1 had no significant effect, The response to NT-3 was blocked by inhibitors of protein kinases, phospholipase C, and serine/threonine protein phosphatase 1 and 2a, Omission of Ca2+ from the extracellular medium prevented the NT-3 effect. Our results indicate that NT-3 stimulates BK channel activity in cortical neurons through a signaling pathway that involves Trk tyrosine kinase, phospholipase C, and protein dephosphorylation and is calcium-dependent. Activation of BK channels may be a major mechanism by which neurotrophins acutely regulate neuronal activity.
引用
收藏
页码:1002 / 1006
页数:5
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