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

Autor: Diana L. Kunze, Mary Hamra, Martin Runciman, Robert S. McNeil
Rok vydání: 1999
Předmět:
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 277:H705-H713
ISSN: 1522-1539
0363-6135
Popis: We used the whole cell open-patch or perforated-patch technique to characterize μ-opioid modulation of Ca2+ current ( I Ca) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neurons. The μ-opiate receptor agonist Tyr-d-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) inhibited I Ca in 95% of neonatal [postnatal day (P)1–P3] nodose neurons. To the contrary, only 64% of juvenile cells (P20–P35) and 61% of adult cells (P60–P110) responded to DAGO. DAGO-mediated inhibition of I Ca was naloxone sensitive, irreversible in the presence of guanosine 5′- O-(3-thiotriphosphate), absent with guanosine 5′- O-(2-thiodiphosphate), and eliminated with pertussis toxin; DAGO’s inhibition of I Ca was G protein mediated. Incubation of neurons with ω-conotoxin GVIA eliminated the effect of DAGO in neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of the current remaining in the presence of ω-conotoxin. In the subset of nodose neurons, aortic baroafferents, the effect of DAGO was concentration dependent, with an IC50 of 1.82 × 10−8 M. DAGO slowed activation of I Ca, but activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, μ-opiate modulation of I Ca in nodose neurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of μ-opioids on baroreceptor afferents provides a basis for the attenuation of the baroreflex that occurs at the level of the nucleus tractus solitarii.
Databáze: OpenAIRE