MECHANISM OF INHIBITION OF CALCIUM CHANNELS IN RAT NUCLEUS-TRACTUS-SOLITARIUS BY NEUROTRANSMITTERS

1 High-threshold Ca2+ channel currents were measured every 15 s follow ing a 200 ms voltage step from -80 mV to 0 mV in order to study the co upling mechanism between neurotransmitter receptors and Ca2+ channels in neurones acutely isolated from the nucleus tractus solitarius (NTS) of the rat. 2 Application of 30 pM baclofen (GABAB receptor agonist) caused 38.9+/-1.2% inhibition of the peak inward Ba2+ current (I-Ba2+) in most NTS cells tested (n = 85 of 88). Somatostatin, 300 nM, also r educed I-Ba2+ by 31.3+/-1.6% in 53 cells of 82 tested. 3 Activation of mu-opioid-, GABA(B)- 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 seduced by tr eatment with pertussis toxin and partially relieved by application of a 50 ms conditioning prepulse to +80 mV. This suggests that a pertussi s toxin-sensitive G-protein was involved in the neurotransmitter-media ted action in the observed inhibition of Ca2+ currents. 5 Intracellula r loading with an antiserum raised against the amino terminus of G(o a lpha) (CC/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-pr otein-mediated pathways are involved in receptor-induced inhibition of Ca2+ currents in the NTS.