Electrophysiological actions of alfentanil: intracellular studies in the rat locus coeruleus neurones.
1. The electrophysiological effects of alfentanil on 156 neurones of the rat locus coeruleus were investigated by use of intracellular recordings from the in vitro brain slice preparation. 2. Bath application of alfentanil (5-100 nM) reversibly decreased the firing rate of all neurones tested in a dose-dependent manner, with an IC50 4.1.nM. 3. Based on inhibition of the spontaneous firing rate, alfentanil was 22 times more potent than morphine. 4. At 100 nM, alfentanil produced a complete inhibition of firing of all neurones tested (n = 62); the inhibition was accompanied by a membrane hyperpolarization 17.0 +/- 0.8 mV (range 6.1-30.3 mV, n = 62) and a reduction in input resistance 26.4 +/- 1.7% (range 6.5-53%, n = 51). 5. The effects of alfentanil were antagonized by naloxone, with a dissociation equilibrium constant of 2.7 +/- 0.4 nM (n = 6). 6. The reversal potential for the alfentanil-induced hyperpolarization was -110 +/- 2 mV (n = 9), which is approximately the potassium equilibrium potential. 7. The alfentanil-induced hyperpolarization was blocked by caesium chloride and barium chloride. 8. These results indicate that alfentanil binds to mu-opioid receptors on the cell membrane of neurones of the locus coeruleus. This leads to opening of the inward-going rectification potassium channels, resulting in the observed hyperpolarization of the membrane.
Chiu
T H
TH
Department of Physiology, National Yang-Ming Medical College, Taipei, Taiwan.
Yeh
M H
MH
Tsai
S K
SK
Mok
M S
MS
D015760:Alfentanil / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism
D017609:Barium Compounds; D002712:Chlorides; D015221:Potassium Channels; D017450:Receptors, Opioid, mu; C024986:barium chloride; D002586:Cesium; D015760:Alfentanil; D009270:Naloxone; D009020:Morphine; C028019:cesium chloride