BARBITURATE DEPRESSION OF CALCIUM-MEDIATED STIMULUS-SECRETION COUPLING IN SYNAPTOSOMES - SPECIES AND STRAIN COMPARISON

Pentobarbital depression of potassium-stimulated 45Ca++ influx was examined in synaptosomes prepared from animal species and strains with reported differences in their sensitivity to pentobarbital sedation. Synaptosomes were isolated from New Zealand, white rabbits, Sprague-Dawley rats, C57/6J mice and DBA/2J mice. Synaptosomes isolated from the various groups were challenged with concentrations of 0.15, 0.30, 0.45 and 0.60 mM pentobarbital in incubation medium and compared with synaptosomes in incubation medium alone to assess the degree of depression of 45Ca++ influx. The results show that pentobarbital significantly depresses 45Ca++ influx to approximately the same extent in all animal groups at concentrations of 0.30 mM and higher. It is concluded that reported in vivo differences in pentobarbital sedative sensitivity between these animal groups does not involve differences in calcium influx. Further, the data show that inhibition of 45Ca++ influx by pentobarbital is generalizable across several animal strains and species and suggest, as we have previously reported, that inhibition of calcium influx across the presynaptic nerve ending may provide a mechanism through which the barbiturates produce sedation. © 1979.