COEXISTENCE OF GABAA AND GABAB RECEPTORS ON A-DELTA-PRIMARY AND C-PRIMARY AFFERENTS

Intracellular recordings from adult rat dorsal root ganglion neurons were performed in vitro and the coexistence of 2 GABA receptors on the membrane of identified A.delta. and C primary afferents was demonstrated. Transient applications of GABA (10-6-10-2 M) evoked dose-dependent depolarizations and increased membrane conductance. The responses were mimicked by muscimol, isoguvacine, THIP [4,5,6,7-tetrahydroisoxazolo[5,4 c]-pyridin-3-ol] and 3-amino-propane sulfonic acid (3 APS); they were blocked by bicuculline and picrotoxin. Pentobarbitone induced an increase of GABA-induced depolarizations. Perfusion of tetraethylammonium (TEA, 7.5 mM) and intracellular injection of Cs+ unmasked the Ca2+ component of action potentials, which appeared as long-lasting plateau depolarizations. Such action potentials were shortened in the presence of methoxyverapamil (D600, 5 .times. 10-6-10-5 M) and in a medium without Ca2+. Prolonged (5-10 min) perfusion of GABA (10-9-10-5 M) shortened the Ca2+ component of action potentials. This effect was mimicked by baclofen (10-7-5 .times. 10-6 M) and muscimol (5 .times. 10-7-10-5 M) and was not affected by bicuculline perfusion (5 .times. 10-6-10-5 M). Isoguvacine (2.5 .times. 10-5 M) did not affect action potential duration. Evidently 2 GABA receptors coexist on the membrane of slow conducting primary afferents: the bicuculline-sensitive GABAA receptor mediates depolarizations and the bicuculline-insensitive GABAB receptor shortens the Ca2+ component of action potentials.