A G Protein Mediates the Inhibition of the Voltage-Dependent Potassium M Current by Muscarine, LHRH, Substance P and UTP in Bullfrog Sympathetic Neurons.

摘要: The involvement of G proteins in the transduction mechanism M current (Im) inhibition by extracellular ligands bullfrog sympathetic neurons was examined using hydrolysis resistant nucleotide analogues GTPgammaS and GDPbetaS. Im recorded large (40 - 60 microm) isolated patch-clamp technique whole-cell configuration, as well from intact ganglion impaled with conventional microelectrodes. In recordings could be without significant loss for 1 h or more provided ATP present patch pipette. Muscarine, D-Ala6-LHRH, substance P UTP reversibly inhibited control neurons, full rapid recovery following agonist washout. Dialysis various concentrations (1 100 microM) affected, a dose-dependent manner, after its brief application. With 50 microM GTPgammaS, became completely irreversible. Similarly, reversibility muscarine reduced abolished iontophoretic injection through second microelectrode into ganglion. itself caused slow, agonist-independent suppression dialysed thus mimicking action. GDPbetaS (100 500 attenuated half magnitude compared to neurons. addition, response given neuron slow increase Im, function dialysis time. Incubation (2 72 h, 4 36 degrees C) ganglions activated pertussis toxin had no effect on muscarine. Toxin injections experimental animals were equally ineffective. contrast additional inward conductance induced D-Ala6-LHRH reversed washout GTPgammaS-dialysed although slowly than results this study indicate that protein, possibly toxin-insensitive, provides common coupling step linking muscarinic, P, receptors current.