Selective activation of G-protein coupled receptors by volatile anesthetics

Abstract

Ion channels and ionotropic neurotransmitter receptors have long been investigated as the principle targets of inhaled volatile anesthetics (VAs), but emerging evidence suggests that G-protein coupled receptors (GPCRs) might also directly interact with VAs. To survey the extent of interaction between VAs and diverse GPCRs, we have turned to the 1000+ member family of olfactory receptors (ORs), taking advantage of their unique expression pattern of a single OR per neuron. Through optical imaging and electrophysiological recordings, we show that different VAs trigger the normal transduction cascade in distinct subsets of cells in a dose-dependant manner. Together with evidence of antagonism by odorants, this selective activation strongly implicates a direct action of VAs upon particular olfactory receptors. The finding that VAs stimulate nearly 8% of olfactory GPCRs suggests that probing related Class A GPCRs may reveal a pool of VA targets whose altered signaling contributes to anesthetic effects.