TY - JOUR T1 - Effects of Volatile Anesthetics on the Direct and Indirect Protein Kinase C-Mediated Enhancement of α1E-Type Ca<sup>2+</sup>Current in <em>Xenopus</em> Oocytes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 360 LP - 369 VL - 293 IS - 2 AU - Ganesan L. Kamatchi AU - Shveta N. Tiwari AU - Marcel E. Durieux AU - Carl Lynch III Y1 - 2000/05/01 UR - http://jpet.aspetjournals.org/content/293/2/360.abstract N2 - The effect of the volatile anesthetics (VAs) halothane (0.59 mM) and isoflurane (0.70 mM) on protein kinase C (PKC)-mediated modulation of α1E type of high-voltage-gated Ca2+ channels was examined in Xenopus oocytes coexpressing m1 muscarinic acetylcholine receptors. Phorbol-12-myristate-13-acetate (PMA) or 1,2-dioctanoyl-sn-glycerol (DOG) was used to activate PKC directly, whereas indirect activation was induced with acetyl-β-methylcholine (MCh). The interaction between PKC activators and VAs was examined by perfusing either VA before, during, or after the administration of PMA, DOG, or MCh. In addition, the effect of VAs was studied after the down-regulation of PKC. The application of VAs inhibited Ba2+ current (IBa), whereas PMA (500 nM), DOG (100 μM), or MCh (1 and 10 μM) markedly potentiated IBa. VAs inhibited PMA- or DOG-enhanced IBa to the same extent as seen in controls. The inhibition of IBa induced by VAs was not reversed by PMA or DOG. The administration of VAs in combination with PMA, DOG, or MCh (1 μM) led to the inhibition ofIBa. MCh (10 μM) counteracted the inhibitory effect of VAs when administered together and reversed the inhibition of IBa produced by VAs. These differences in the responses between PMA and MCh (10 μM) may be based on the involvement of various pools of PKC. It is suggested 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 partially blocked. It is possible that some PKC isoforms may not be a direct target of VAs. The American Society for Pharmacology and Experimental Therapeutics ER -