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J. Biol. Chem., Vol. 278, Issue 18, 16271-16279, May 2, 2003
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From the Speed and reliability of synaptic transmission
are essential for information coding in neuronal networks and require
the presence of clustered neurotransmitter receptors at the plasma
membrane in precise apposition to presynaptic terminals. Receptor
clusterization is the result of highly regulated processes involving
functional and structural proteins. Among the structural elements,
microtubules are known to play a crucial role in anchoring of
Declusterization of GABAA Receptors Affects the
Kinetic Properties of GABAergic Currents in Cultured Hippocampal
Neurons*
,,§,
, and**
Neuroscience Programme and Istituto
Nazionale Fisica della Materia Unit, International School for Advanced
Studies, Via Beirut 2-4, Trieste 34014, Italy and the ¶ Department
of Biophysics, Wroclaw Medical University, ul. Chalubinskiego
10, Wroclaw 50-368, Poland
-aminobutyric acid, type A (GABAA) receptors. Here
we show that microtubule depolymerization with nocodazole induces the
declusterization of GABAA receptors and modifies the
kinetic properties of GABAergic currents in cultured hippocampal
neurons. In particular, this drug, applied either in the bath or via
the patch pipette, induced the acceleration of the onset kinetics of
miniature inhibitory postsynaptic currents (mIPSCs) without
significantly affecting their frequency, thus suggesting a main
postsynaptic site of action. After nocodazole treatment, current
responses to ultrafast applications of GABA exhibited a faster
rise time and an accelerated onset of desensitization. A quantitative
analysis of GABA-evoked currents and model simulations suggest that
declusterization affects the gating properties of GABAA
receptors. In particular, a faster entry into the desensitized state of
declustered GABAA receptors may account for the changes in
the kinetic properties of mIPSCs after nocodazole treatment. Hence it
appears that the clustered condition of GABAA receptors
contributes in shaping GABAergic currents.
*
This work was supported in part by the Ministero
dell'Istruzione, dell'Universita' e della Ricerca (Grant COFI 2001 to E. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by the Polish Committee for Scientific Research
(Grant 6P04A-001-19).
**
To whom correspondence should be addressed. Tel.: 39-040-378-7223;
Fax: 39-040-378-7528; E-mail: cher@sissa.it.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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