Essential function of α-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse

被引：73

作者：

Hinds, HL

Goussakov, I

Nakazawa, K

Tonegawa, S

Bolshakov, VY

机构：

[1] MIT Neurosci Res Ctr, RIKEN, Picower Ctr Learning & Memory, Howard Hughes Med Inst,Dept Biol, Cambridge, MA 02139 USA

[2] MIT Neurosci Res Ctr, RIKEN, Picower Ctr Learning & Memory, Howard Hughes Med Inst,Dept Cognit Sci, Cambridge, MA 02139 USA

[3] Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02478 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2003年 / 100卷 / 07期

关键词：

D O I：

10.1073/pnas.0530202100

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：

A significant fraction of the total calcium/calmodulin-dependent protein kinase II (CaMKII) activity, in neurons is associated with synaptic connections and is present in nerve terminals, thus suggesting a role for CaMKII in neurotransmitter release. To determine whether CaMKII regulates neurotransmitter release, we generated and analyzed knockout mice in which the dominant a-isoform of CaMKII was specifically deleted from the presynaptic side of the CA3-CA1 hippocampal synapse. Conditional CA3 a-CaMKII knockout mice exhibited an unchanged basal probability of neurotransmitter release at CA3-CA1 synapses but showed a significant enhancement in the activity-dependent increase in probability of release during repetitive presynaptic stimulation, as was shown with the analysis of unitary synaptic currents. These data indicate that alpha-CaMKII serves as a negative activity-dependent regulator of neurotransmitter release at hippocampal synapses and maintains synapses in an optimal range of release probabilities necessary for normal synaptic operation.

引用

页码：4275 / 4280

页数：6

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