LANTHANUM-MEDIATED MODIFICATION OF GABA(A), RECEPTOR DEACTIVATION, DESENSITIZATION AND INHIBITORY SYNAPTIC CURRENTS IN RAT CEREBELLAR NEURONS

1. We investigated La3+ effects on recombinant and native gamma-aminob utyric acid A (GABA(A)) receptors using rapid agonist applications and on inhibitory synaptic currents (IPSCs) in granule and stellate neuro ns of rat cerebellar slices. 2. Rapid desensitization of currents elic ited by 200 ms pulses of 1 mM GABA to small lifted cells transfected w ith alpha 1 beta 3 gamma 2 cDNAs was greatly decreased by the coapplic ation of 100 mu M LaCl3. 3. GABA responses were unaffected when coappl ication lasted only 2 ms. In contrast, with LaCl3 pre-perfusion, a sig nificant slowing of deactivation in response to 2 ms applications was observed. LaCl3 pre-perfusion also prolonged the duration of responses to 20 mM taurine. 4. Outside-out patches excised from cells transfect ed with alpha 1 beta 3 gamma 2 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 LaCl3. 5. LaCl3 depressed the peak amplitude without affecting the slow deac tivation and desensitization of GABA responses in cells transfected wi th alpha 6 beta 3 gamma 2 and alpha 6 beta 3 delta cDNAs. No significa nt difference in La3+ modulation of GABA-gated currents was observed b etween alpha 1 beta 3 gamma 2 and alpha 1 beta 3 delta receptors. 6. T he effects of LaCl3 on deactivation and desensitization of GABA respon ses observed in nucleated patches excised from rat cerebellar granule and stellate neurons were comparable to those in the cells transfected with alpha 1 beta 3 gamma 2 cDNAs. In addition, La3+ clearly prolonge d the spontaneous IPSC time course without changing the amplitude. 7. Our results indicate that La3+ has a dual action on GABA-gated current s: it decreases desensitization and increases channel opening duration . These actions depend on receptor subunit composition and contribute to the prolongation of IPSCs.