GABA increases refractoriness of adult rat dorsal column axons

We applied randomized double pulse stimulation for assessing the effects of GABA and a GABA(A) antagonist on compound action potentials in dorsal colu mn axons isolated from adult rat. We stimulated the axons with double pulse s at 0.2 Hz and randomly varied interpulse intervals between 3, 4, 5, 8, 10 , 20, 30, 50 and 80 ms. Action potentials were measured using glass micropi pettes. The first pulse was used to condition the response activated by the second test pulse. Concentrations of GABA of 1 mM, 100 mu M and 10 mu M di d not affect action potential amplitudes or latencies activated by conditio ning pulses. In the control studies, before drug administration, test pulse s induced response amplitudes that were significantly decreased at 3-, 4- a nd 5-ms interpulse intervals. The test action potential amplitudes were 84. 6 +/- 2.5%, 89.0 +/- 3.9% and 93.3 +/- 3.6% (mean +/- S.E.M.) of conditioni ng pulse levels, respectively. At 3-ms interpulse intervals, test response latencies were prolonged to 104.3 +/- 1.0%, but were unchanged at the other interpulse intervals. The 10 mu M, 100 mu M and 1 mM concentrations of GAB A affected test response amplitudes. Application of 100 mu M GABA reduced t he amplitudes of test responses at 3-, 4-, 5- and 8-ms interpulse intervals , to 59.2 +/- 3.0%, 70.0 +/- 3.0%, 80.2 +/- 1.1% and 88.6 +/- 3.6% of the c onditioning pulse amplitudes, respectively. At both 100 mu M and 1 mM conce ntrations, GABA significantly prolonged the latencies of test responses. Tr eatment with 100 mu M GABA prolonged the latencies of test responses at 3-, 4- and 5-ms interpulse intervals, to 119.3 +/- 3.1%, 107.3 +/- 2.8% and 10 5.5 +/- 2.5% of conditioning pulse latencies, respectively. The addition of 100 mu M bicuculline methochloride, a GABA(A) antagonist, eliminated the e ffects of 100 mu M GABA. The combined application of GABA and bicuculline ( both 100 mu M) did not affect amplitudes or latencies of test responses. These results suggest that GABA(A) receptor subtypes are present on the spi nal dorsal column axons of adult rat, and that they modulate the excitabili ty of the axons. The randomized double pulse methods reveal that GABA incre ases refractoriness of adult rat dorsal column axons. (C) 1999 IBRO. Publis hed by Elsevier Science Ltd.