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Kinetics of AMPA-type glutamate receptor channels in rat caudate-putamen neurones show a wide range of desensitization but distinct recovery characteristics


Dr K. Jahn, as above.


α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor channels of rat caudate-putamen neurones were studied by ultrafast application of agonists to outside-out vesicles taken from medium-sized spiny neurones in thin slices. Upon application of 10 m m glutamate for 50 ms, fast rising and desensitizing currents were activated. Ten to 90% rise time values were ≈ 0.5 ms. Dose–response studies revealed an EC50 of 0.63 m m glutamate. In double logarithmic coordinates, the curve had a maximal slope between 1.33 and 1.85 at low concentrations, indicating at least two binding sites for glutamate. Rise time increased with low agonist concentrations, whereas desensitization kinetics showed only a weak dependence on concentration. The time constant of desensitization was fitted with one exponential and ranged between 2 and 11 ms, with a mean of 6.19 ± 2.31 ms (n = 239). Following brief glutamate pulses (1 ms) currents decayed with time constants of 2.7 ± 0.23 ms (n = 12). Recovery from desensitization was investigated by double-pulse experiments. Recovery time constants fell in two subgroups with respective mean values of 110.6 ± 14.2 ms (n = 8) and 288.6 ± 33.2 ms (n = 8). By adding low glutamate concentrations to the bath solution, predesensitization of AMPA-type receptors without channel opening could be shown. A 50% reduction in control amplitude was achieved with 5.2 ± 2.1 μm (n = 22) glutamate in the background. We hypothesize a circular reaction scheme with at least two binding sites for glutamate to describe activation, desensitization and recovery from desensitization in rat caudate-putamen neurones.