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Lanthanum‐mediated modification of GABA A receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons
Author(s) -
Zhu Wei Jian,
Wang Jian Feng,
Corsi Lorenzo,
Vicini Stefano
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.647bg.x
Subject(s) - inhibitory postsynaptic potential , desensitization (medicine) , gabaa receptor , biophysics , chemistry , cerebellum , agonist , receptor , nifedipine , transfection , taurine , medicine , endocrinology , biology , neuroscience , biochemistry , calcium , amino acid , organic chemistry , gene
1 We investigated La 3+ effects on recombinant and native γ‐aminobutyric acid A (GABA A ) receptors using rapid agonist applications and on inhibitory synaptic currents (IPSCs) in granule and stellate neurons of rat cerebellar slices. 2 Rapid desensitization of currents elicited by 200 ms pulses of 1 mM GABA to small lifted cells transfected with α1β3γ2 cDNAs was greatly decreased by the coapplication of 100 μ m LaCl 3 . 3 GABA responses were unaffected when coapplication lasted only 2 ms. In contrast, with LaCl 3 pre‐perfusion, a significant slowing of deactivation in response to 2 ms applications was observed. LaCl 3 pre‐perfusion also prolonged the duration of responses to 20 mM taurine. 4 Outside‐out patches excised from cells transfected with α1β3γ2 subunit cDNAs were briefly exposed to a saturating concentration of GABA, eliciting a transient activation of single channel currents with a main conductance of 30 pS. Opening and burst durations increased by pre‐equilibration of patches with LaCl 3 . 5 LaCl 3 depressed the peak amplitude without affecting the slow deactivation and desensitization of GABA responses in cells transfected with α6β3γ2 and α6β3δ cDNAs. No significant difference in La 3+ modulation of GABA‐gated currents was observed between α1β3γ2 and α1β3δ receptors. 6 The effects of LaCl 3 on deactivation and desensitization of GABA responses observed in nucleated patches excised from rat cerebellar granule and stellate neurons were comparable to those in the cells transfected with α1β3γ2 cDNAs. In addition, La 3+ clearly prolonged the spontaneous IPSC time course without changing the amplitude. 7 Our results indicate that La 3+ has a dual action on GABA‐gated currents: it decreases desensitization and increases channel opening duration. These actions depend on receptor subunit composition and contribute to the prolongation of IPSCs.