Morphine decreases the voltage sensitivity of slow sodium channels.
Cell membrane recordings were made in conditions of voltage clamping with tight attachment of the microelectrode-patch clamping--to study the effects of morphine on tetrodotoxin-resistant (TTXr) sodium channels in rat spinal ganglion neurons in culture. The effects of a number of biologically active substances which regulate the receptor-mediated actions of morphine were studied. The effects of morphine were found to involve a chain of sequential reactions leading to decreases in the transfer of effective charge (Zeff) by the activatory gate system of TTXr sodium channels, depending on the concentration of agonist in the extracellular solution. A value of 8 nM was obtained for KD. with a Hill coefficient of X = 0.5. Non-specific antagonists of opioid receptors blocked the actions of morphine; these included ouabain at a concentration of 100 microM. An inhibitor, and activator, and a blocker of G-proteins had no effect on the effective charge. These data provide evidence that morphine decreases the voltage sensitivity of TTXr sodium channels.
Krylov
B V
BV
I.P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg.
Derbenev
A V
AV
Podzorova
S A
SA
Lyudyno
M I
MI
Kuz'min
A V
AV
Izvarina
N L
NL
D000818:Animals; D002478:Cells, Cultured; D004351:Drug Resistance; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology; D008959:Models, Neurological; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D015222:Sodium Channels; D009270:Naloxone; D013779:Tetrodotoxin; D010042:Ouabain; D009020:Morphine; D000254:Sodium-Potassium-Exchanging ATPase