Declusterization of GABAA receptors affects the kinetic properties of GABAergic currents in cultured hippocampal neurons.
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 gamma-aminobutyric acid, type A (GABA(A)) receptors. Here we show that microtubule depolymerization with nocodazole induces the declusterization of GABA(A) 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 GABA(A) receptors. In particular, a faster entry into the desensitized state of declustered GABA(A) receptors may account for the changes in the kinetic properties of mIPSCs after nocodazole treatment. Hence it appears that the clustered condition of GABA(A) receptors contributes in shaping GABAergic currents.
Petrini
Enrica Maria
EM
Neuroscience Programme and Istituto Nazionale Fisica della Materia Unit, International School for Advanced Studies, Via Beirut 2-4, Trieste 34014, Italy.
Zacchi
Paola
P
Barberis
Andrea
A
Mozrzymas
Jerzy W
JW
Cherubini
Enrico
E
D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D015739:Nocodazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D015739:Nocodazole