Opioids inhibit lateral amygdala pyramidal neurons by enhancing a dendritic potassium current.
Pyramidal neurons in the lateral amygdala discharge trains of action potentials that show marked spike frequency adaptation, which is primarily mediated by activation of a slow calcium-activated potassium current. We show here that these neurons also express an alpha-dendrotoxin- and tityustoxin-Kalpha-sensitive voltage-dependent potassium current that plays a key role in the control of spike discharge frequency. This current is selectively targeted to the primary apical dendrite of these neurons. Activation of micro-opioid receptors by application of morphine or d-Ala(2)-N-Me-Phe(4)-Glycol(5)-enkephalin (DAMGO) potentiates spike frequency adaptation by enhancing the alpha-dendrotoxin-sensitive potassium current. The effects of micro-opioid agonists on spike frequency adaptation were blocked by inhibiting G-proteins with N-ethylmaleimide (NEM) and by blocking phospholipase A(2). Application of arachidonic acid mimicked the actions of DAMGO or morphine. These results show that micro-opioid receptor activation enhances spike frequency adaptation in lateral amygdala neurons by modulating a voltage-dependent potassium channel containing Kv1.2 subunits, through activation of the phospholipase A(2)-arachidonic acid-lipoxygenases cascade.
Faber
E S Louise
ES
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.
Sah
Pankaj
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009294:Narcotics / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism
D009294:Narcotics; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017450:Receptors, Opioid, mu