The modulation of GIRK channels by halothane is essentially determined by its C terminus

摘要

G protein-activated K~+ channels (GIRK1 or Kir3) are targets for volatile anaesthetics. The modulation by halothane of channels coexpressed with the m_2 acetylcholine (ACh) receptor in Xenopus oocytes is characterized by inhibition of the agonist activated current through GIRK1~(FI37S) and GIRK2 channels. In contrast, in the absence of ACh, halothane is able to induce GIRK1~(FI37S) mediated currents. Such an increase in background currents by halothane was never observed with GIRK2 channels. Deleting the C terminus of GIRK2 (GIRK2~(DELTA356)) rendered the channel insensitive against the inhibition by halothane; in contrast, like GIRKl~(FI37S) channels GIRK2~(DELTA356)) channels were activated by halothane in the absence of an agonist. Because the C terminus is crucial for these effects, an interaction of halothane with the channel seems to be involved in the mechanism of GIRK current modulation.