Mechanism of inhibition of calcium channels in rat nucleus tractus solitarius by neurotransmitters.

1. High-threshold Ca2+ channel currents were measured every 15 s following a 200 ms voltage step from -80 mV to 0 mV in order to study the coupling mechanism between neurotransmitter receptors and Ca2+ channels in neurones acutely isolated from the nucleus tractus solitarius (NTS) of the rat. 2. Application of 30 microM baclofen (GABAB receptor agonist) caused 38.9 +/- 1.2% inhibition of the peak inward Ba2+ current (IBa2+) in most NTS cells tested (n = 85 of 88). Somatostatin, 300 nM, also reduced IBa2+ by 31.3 +/- 1.6% in 53 cells of 82 tested. 3. Activation of mu-opioid-, GABAB- or somatostatin-receptors inhibited both N- and P/Q-type Ca2+ channels. 4. The inhibition of Ca2+ currents by DAMGo (mu-opioid receptor agonist), baclofen and somatostatin was reduced by treatment with pertussis toxin and partially relieved by application of a 50 ms conditioning prepulse to +80 mV. This suggests that a pertussis toxin-sensitive G-protein was involved in the neurotransmitter-mediated action in the observed inhibition of Ca2+ currents. 5. Intracellular loading with an antiserum raised against the amino terminus of Go alpha (GC/2) markedly attenuated the somatostatin-induced inhibition, but did not block the DAMGO- and baclofen-induced inhibition. 6. These findings suggest at least two different pertussis toxin-sensitive G-protein-mediated pathways are involved in receptor-induced inhibition of Ca2+ currents in the NTS.