Opioid inhibition of GABAergic neurotransmission in mechanically isolated rat periaqueductal gray neurons.
The descending pain control system is activated by opioid peptides mainly at the midbrain periaqueductal gray (PAG). Although activation of presynaptic opioid receptors has been reported to inhibit gamma-aminobutyric acid (GABA) release, the exact electrophysiological mechanisms are controversial. To elucidate the mechanisms involved in the opioid modulation of presynaptic GABA release, we isolated single PAG neurons with functionally intact synaptic terminals by a mechanical dissociation in the absence of enzyme. With the conventional whole-cell recording mode under the voltage-clamp conditions, the spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were recorded. Bicuculline completely and reversibly blocked mIPSCs. A specific mu-opioid agonist, [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), reversibly reduced the frequency of mIPSCs without any alteration of amplitude. The inhibitory effect of DAMGO was blocked by N-ethylmaleimide. Blockade of presynaptic Ca(2+) influx by cadmium or depletion of extracellular Ca(2+) did not alter the DAMGO inhibition. In addition, K(+) channels blockers, Ba(2+) or 4-aminopyridine, did not affect the DAMGO effect. The present study indicates that activation of presynaptic mu-opioid receptors coupled to G-proteins inhibits GABA release through unknown intracellular mechanisms downstream of Ca(2+) influx.
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, South Korea.
Eu-Teum
ET
Hahm
Jong-Ju
JJ
Lee
Byung-Il
BI
Min
Young-Wuk
YW
Cho
D000818:Animals; D066298:In Vitro Techniques; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009292:Narcotic Antagonists; D005680:gamma-Aminobutyric Acid