Activation of mu opioid receptors inhibits transient high- and low-threshold Ca2+ currents, but spares a sustained current.
Opioids and opiates decrease the duration of action potentials and the amount of neurotransmitter released from sensory neurons. The mu-type opioid receptor, the binding site for morphine, is thought to act exclusively on K+ channels. Here, we show that activation of the mu receptor inhibits Ca2+ channels in rat sensory neurons; the effect is blocked by a mu antagonist and is not mimicked by kappa or delta receptor agonists. Both low-threshold (T-type) and high-threshold Ca2+ currents are partially suppressed. omega-Conotoxin-sensitive and omega-conotoxin-insensitive, high-threshold Ca2+ currents are inhibited. The kinetic effect on high-threshold current is like that caused by diminished rest potential: the transient component is selectively lost, whereas the sustained component is spared.
Schroeder
J E
JE
Department of Cell Biology and Physiology, Washington University, St. Louis, Missouri 63110.
Fischbach
P S
PS
Zheng
D
D
McCleskey
E W
EW
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004553:Electric Conductivity; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D004745:Enkephalins; D008978:Mollusk Venoms; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C024524:beta-funaltrexamine; D020881:Enkephalin, D-Penicillamine (2,5)-; D020866:omega-Conotoxin GVIA