THE CALCINEURIN INHIBITOR CYCLOSPORINE-A CYCLOPHILIN-A COMPLEX REDUCES DESENSITIZATION OF GABA(A)-MEDIATED RESPONSES IN ACUTELY DISSOCIATEDRAT HIPPOCAMPAL-NEURONS

The effects of the selective inhibitor of calcineurin, cyclosporin A-c yclophilin A (CC) complex on the desensitization kinetics of GABA(A) r eceptors was studied in acutely dissociated hippocampal neurons, using the patch clamp technique in the whole cell configuration. In control conditions, the decay of GABA-evoked current could be fitted by a bie xponential function having time constants of 0.65 +/- 0.24 s and 3.75 +/- 2 s. The plateau to peak ratio was 0.087 +/- 0.034. Recovery from desensitization was obtained in more than 2 min. In cells dialyzed wit h the CC complex, the decay of the currents could be fitted with the s um of two exponentials having time constants similar to controls (0.81 +/- 0.47 s and 3.62 +/- 2.1 s), but the percentage of the fast compon ent was smaller. The plateau to peak ratio was significantly larger th an control (0.185 +/- 0.07). With CC complex, recovery from desensitiz ation was completed in almost 30 s. The cyclosporin A derivative PSC 8 33, which does not inhibit calcineurin, did not affect desensitization kinetics. These results suggest that phosphatase 2B regulates desensi tization of GABA(A) receptors.