Modulation of Ca2+ channel current by mu opioid receptors in prefrontal cortex pyramidal neurons in rats

Acta Neurobiol Exp (Wars). 2008;68(1):10-25. doi: 10.55782/ane-2008-1667.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Animals, Newborn
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Calcium Channels / radiation effects
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Isoquinolines / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Patch-Clamp Techniques / methods
  • Prefrontal Cortex / cytology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, mu / physiology*
  • Sulfonamides / pharmacology
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Analgesics, Opioid
  • Calcium Channel Blockers
  • Calcium Channels
  • Enzyme Inhibitors
  • Isoquinolines
  • Narcotic Antagonists
  • Receptors, Opioid, mu
  • Sulfonamides
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • 9-(tetrahydro-2-furyl)-adenine
  • Naloxone
  • omega-Conotoxin GVIA
  • Adenine
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide