Dynorphin A decreases voltage-dependent calcium conductance of mouse dorsal root ganglion neurones.
The actions of the opioid peptides dynorphin A and (Leu)enkephalin were assessed on calcium-dependent action potentials and inward calcium currents recorded from somata of mouse dorsal root ganglion (d.r.g.) neurones grown in primary dissociated cell culture. Dynorphin A and (Leu)enkephalin decreased the duration of somatic calcium-dependent action potentials in a portion of d.r.g. neurones impaled with potassium acetate-filled micropipettes. When substantial potassium conductance was blocked by intracellular injection of caesium acetate, d.r.g. neurones continued to respond to dynorphin A but responses to (Leu)enkephalin were abolished. In voltage-clamp experiments, dynorphin A but not (Leu)enkephalin reduced the magnitude of inward calcium currents. Dynorphin A responses were blocked by the opiate antagonist naloxone. The dynorphin A effect was due to reduction of voltage-dependent calcium conductance since dynorphin A reduced depolarization-evoked inward currents but did not alter membrane conductance following blockade of calcium channels by cadmium, and because dynorphin A reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance. Dynorphin A binds with high affinity to kappa-opioid receptors. (Leu)enkephalin, which has affinity for both mu- and delta-receptors but not for kappa-opioid receptors, was without effect on calcium conductance. Therefore, we suggest that kappa-receptors are coupled to voltage-dependent calcium-channels and that binding of dynorphin A produces a decrease of calcium current.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004399:Dynorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D013997:Time Factors
D007473:Ion Channels; D004743:Enkephalin, Leucine; D004399:Dynorphins; D002118:Calcium