Modulation of Ca2+ channel current by mu opioid receptors in prefrontal cortex pyramidal neurons in rats.
Our work assesses the effects of mu opioid receptor activation on high-threshold Ca2+/Ba2+ currents in freshly dispersed pyramidal neurons of the medial prefrontal cortex in rats. Application of the specific mu receptor agonist (D-Ala2+, N-Me-Phe4+, Gly5+-ol)-enkephalin (DAMGO) at 1 microM decreased Ca2+ current amplitudes from 0.72 to 0.49 nA. The effect was abolished by naloxone and omega-Conotoxin GVIA. Inhibition was not abolished by strong depolarisation of the cell membrane. In addition, a macroscopic Ba2+ current recorded in cell-attached configuration was inhibited when DAMGO was applied outside the patch pipette. An adenylyl cyclase inhibitor (SQ 22536) and a protein kinase A inhibitor (H-89) decreased Ca2+ current amplitude. Moreover, the inhibitory effect of mu opioid receptors on Ca2+ currents required the activation of protein kinase A. We conclude that activation of mu opioid receptors in medial prefrontal cortex pyramidal neurons inhibits N type Ca2+ channel currents, and that protein kinase A is involved in this transduction pathway.
Rola
Rafał
R
Department of Physiology and Department of Experimental and Clinical Physiology, The Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-325 Warsaw, Poland.
Jarkiewicz
Michał
M
Szulczyk
Paweł
P
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D013449:Sulfonamides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C017759:9-(tetrahydro-2-furyl)-adenine; D009270:Naloxone; D020866:omega-Conotoxin GVIA; D000225:Adenine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide