Gl. Kamatchi et al., Effects of volatile anesthetics on the direct and indirect protein kinase C-mediated enhancement of alpha 1E-type Ca2+ current in Xenopus oocytes, J PHARM EXP, 293(2), 2000, pp. 360-369
Citations number
39
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
The effect of the volatile anesthetics (VAs) halothane (0.59 mM) and isoflu
rane (0.70 mM) on protein kinase C (PKC)-mediated modulation of alpha 1E ty
pe of high-voltage-gated Ca2+ channels was examined in Xenopus oocytes coex
pressing m1 muscarinic acetylcholine receptors. Phorbol-12-myristate-13-ace
tate (PMA) or 1,2-dioctanoyl-sn-glycerol (DOG) was used to activate PKC dir
ectly, whereas indirect activation was induced with acetyl-beta-methylcholi
ne (MCh). The interaction between PKC activators and VAs was examined by pe
rfusing either VA before, during, or after the administration of PMA, DOG,
or MCh. In addition, the effect of VAs was studied after the downregulation
of PKC. The application of VAs inhibited Ba2+ current (I-Ba), whereas PMA
(500 nM), DOG (100 mu M), or MCh (1 and 10 mu M) markedly potentiated I-Ba.
VAs inhibited PMA- or DOG-enhanced I-Ba to the same extent as seen in cont
rols. The inhibition of I-Ba induced by VAs was not reversed by PMA or DOG.
The administration of VAs in combination with PMA, DOG, or MCh (1 mu M) le
d to the inhibition of I-Ba. MCh (10 mu M) counteracted the inhibitory effe
ct of VAs when administered together and reversed the inhibition of I-Ba pr
oduced by VAs. These differences in the responses between PMA and MCh (10 m
u M) may be based on the involvement of various pools of PKC. It is suggest
ed that VAs act directly at the membrane, because they blocked the membrane
-based action of PMA, whereas the receptor-based action of MCh was only par
tially blocked. It is possible that some PKC isoforms may not be a direct t
arget of VAs.