Modulation of the developing rat sympathetic GABAA receptor by Zn++, benzodiazepines, barbiturates and ethanol

We have examined the effects of GABA and several GABAA receptor modulators on isolated rat (1-160 days) superior cervical ganglion (SCG) neurons with whole-cell recordings. The neurons were sensitive to GABA within 12 h after birth, and the relationship between the current amplitude and GABA concentration (GABA50 = 19 microM) in these newborn neurons was fitted with a Hill coefficient close to 1.0. Adult neurons, on the other hand, had a GABA50 value of 30 microM, and the slope was steeper and fitted with a Hill coefficient of 1.6. Unlike the results of previous studies in cultured SCG neurons, we found that the concentration of Zn++ that reduced the response by 50% was 37 +/- 12 microM in newborns and 43 +/- 6 microM in adults. Bicuculline (10 microM) inhibited the current by 41 +/- 6% and 36 +/- 11% in newborn and adult neurons, respectively. With 5 microM GABA, diazepam and pentobarbital potentiated the response in newborn and adult neurons. No changes were found in the sensitivity of the receptor for these ligands, but their efficacy was enhanced 2-fold during development. Diazepam shifted the relationship between GABA and the response to the left in all the neurons studied. Ethanol (40 mM) reduced the amplitude of the GABA current to 64 +/- 12% of control in newborn neurons and to 85 +/- 4% in adult neurons. The inhibitory effect of 100 mM ethanol on the GABA current was noncompetitive. Addition of a very large concentration of ethanol (850 mM) to newborn neurons potentiated the response to 164 +/- 13% of control.(ABSTRACT TRUNCATED AT 250 WORDS)