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

共 44 条

[11] Genetics of synaptic vesicle function:: Toward the complete functional anatomy of an organelle [J].

Fernández-Chacón, R ;

Südhof, TC .

ANNUAL REVIEW OF PHYSIOLOGY, 1999, 61 :753-776

[12] Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro [J].

Fisahn, A ;

Pike, FG ;

Buhl, EH ;

Paulsen, O .

NATURE, 1998, 394 (6689) :186-189

[13] Autophosphorylation at Thr286 of the α calcium-calmodulin kinase II in LTP and learning [J].

Giese, KP ;

Fedorov, NB ;

Filipkowski, RK ;

Silva, AJ .

SCIENCE, 1998, 279 (5352) :870-873

[14] INHIBITION OF CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE IN DROSOPHILA DISRUPTS BEHAVIORAL PLASTICITY [J].

GRIFFITH, LC ;

VERSELIS, LM ;

AITKEN, KM ;

KYRIACOU, CP ;

DANHO, W ;

GREENSPAN, RJ .

NEURON, 1993, 10 (03) :501-509

[15] SITE-SPECIFIC RECOMBINATION BY THE BACTERIOPHAGE-P1 LOX-CRE SYSTEM - CRE-MEDIATED SYNAPSIS OF 2 LOX SITES [J].

HAMILTON, DL ;

ABREMSKI, K .

JOURNAL OF MOLECULAR BIOLOGY, 1984, 178 (02) :481-486

[16] THE PROBABILITY OF TRANSMITTER RELEASE AT A MAMMALIAN CENTRAL SYNAPSE [J].

HESSLER, NA ;

SHIRKE, AM ;

MALINOW, R .

NATURE, 1993, 366 (6455) :569-572

[17]

Hinds HL, 1998, LEARN MEMORY, V5, P344

[18] Estimating the distribution of synaptic reliabilities [J].

Huang, EP ;

Stevens, CF .

JOURNAL OF NEUROPHYSIOLOGY, 1997, 78 (06) :2870-2880

[19] TARGETED DISRUPTION OF THE MHC CLASS-II AA GENE IN C57BL/6 MICE [J].

KONTGEN, F ;

SUSS, G ;

STEWART, C ;

STEINMETZ, M ;

BLUETHMANN, H .

INTERNATIONAL IMMUNOLOGY, 1993, 5 (08) :957-964

[20] MOLECULAR-CLONING OF A BRAIN-SPECIFIC CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE [J].

LIN, CR ;

KAPILOFF, MS ;

DURGERIAN, S ;

TATEMOTO, K ;

RUSSO, AF ;

HANSON, P ;

SCHULMAN, H ;

ROSENFELD, MG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (16) :5962-5966

← 1 2 3 4 5 →