Figure 2.

Modeling GABA receptor-mediated responses in the cerebellar glomerulus. (A) Schematic representation of the kinetic scheme for α₁ and α₆ subunit-containing receptors (modified from Pugh and Raman, 2005). The traces (continuous lines) show responses to brief and long 1 mM GABA pulses (taken from Tia et al., 1996). The simultaneous fitting of the decay phase of the α₆ response to a fast (1 ms) GABA neurotransmitter pulse (1 mM) and of the almost constant response to a long (200 ms) GABA neurotransmitter pulse (1 mM) is shown (dashed lines) (see Methods and Table 3 for details). (B) The simulated eIPSC generated by the model at 0 mV in response to a 1 ms GABA pulse shows amplitude and kinetics reproducing experimental eIPSCs. The contribution of the α₁ and α₆ components in the eIPSC is shown, revealing that the α₁ receptors account for the direct response while the α₆ receptors account for the indirect response (dashed lines). (C) The simulations show the impact of changing pI (from 0.42 to 0.64) on the GABAergic response to a train of impulses at 100 Hz. The pI increase changes the profile of GABA concentration (in particular, the first peak of GABA concentration is enhanced) modifying the kinetic states of α₁ and α₆ responses (O, C, and D indicate the sum of all the open, closed and desensitized states for each receptor type). The α₁ is more affected than α₆ response by pI, since α₆ receptors reacts slowly and tends to saturate. The associated changes in the α₁ and α₆ currents are shown at the bottom.