Modulation of high-voltage activated Ca2+ channels in the rat periaqueductal gray neurons by mu-type opioid agonist.
The effect of mu-type opioid receptor agonist, D-Ala2,N-MePhe4,Gly5-ol-enkephalin (DAMGO), on high-voltage-activated (HVA) Ca2+ channels in the dissociated rat periaqueductal gray (PAG) neurons was investigated by the use of nystatin-perforated patch recording mode under voltage-clamp condition. Among 188 PAG neurons tested, the HVA Ca2+ channels of 38 neurons (32%) were inhibited by DAMGO (DAMGO-sensitive cells), and the other 80 neurons (68%) were not affected by DAMGO (DAMGO-insensitive cells). The N-, P-, L-, Q-, and R-type Ca2+ channel components in DAMGO-insensitive cells shared 26.9, 37.1, 22.3, 7.9, and 5.8%, respectively, of the total Ca2+ channel current. The channel components of DAMGO-sensitive cells were 45.6, 25.7, 21.7, 4.6, and 2.4%, respectively. The HVA Ca2+ current of DAMGO-sensitive neurons was inhibited by DAMGO in a concentration-, time-, and voltage-dependent manner. Application of omega-conotoxin-GVIA occluded the inhibitory effect of DAMGO approximately 70%. So, HVA Ca2+ channels inhibited by DAMGO were mainly the N-type Ca2+ channels. The inhibitory effect of DAMGO on HVA Ca2+ channels was prevented almost completely by the pretreatment of pertussis toxin (PTX) for 8-10 h, suggesting that DAMGO modulation on N-type Ca2+ channels in rat PAG neurons is mediated by PTX-sensitive G proteins. These results indicate that mu-type opioid receptor modulates N-type HVA Ca2+ channels via PTX-sensitive G proteins in PAG neurons of rats.
Kim
C J
CJ
Department of Physiology, Kyung Hee University College of Medicine, Seoul, Korea.
Rhee
J S
JS
Akaike
N
N
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009761:Nystatin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004745:Enkephalins; D007476:Ionophores; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009761:Nystatin; D019204:GTP-Binding Proteins