Opioid modulation of calcium current in cultured sensory neurons: mu-modulation of baroreceptor input

We used the whole cell open-patch or perforated-patch technique to characte rize mu-opioid modulation of Ca2+ current (I-Ca) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neuron s. The mu-opiate receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DA GO) inhibited I-Ca in 95% of neonatal [postnatal day (P)1-P3] nodose neuron s. To the contrary, only 64% of juvenile cells (P20-P35) and 61% of adult c ells (F60-P110) responded to DAGO. DAGO-mediated inhibition of I-Ca was nal oxone sensitive, irreversible in the presence of guanosine 5'-O-(3-thiotrip hosphate), absent with guanosine 5'-O-(2-thiodiphosphate), and eliminated w ith pertussis toxin; DAGO's inhibition of I-Ca was G protein mediated. Incu bation of neurons with omega-conotoxin GVIA eliminated the effect of DAGO i n neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of th e current remaining in the presence of omega-conotoxin. In the subset of no dose neurons, aortic baroafferents, the effect of DAGO was concentration de pendent, with an IC50 of 1.82 X 10(-8) M. DAGO slowed activation of I-Ca, b ut activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, mu-opiate modulation of I-Ca in nodose n eurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of mu-opioids on baroreceptor afferents provides a basis for the attenuation of the baroref lex that occurs at the level of the nucleus tractus solitarii.