title: Compound 48/80 blocks transmission and increases the excitability of ganglion neurons.
abstract: Compound 48/80 (5.0-50 micrograms/ml) significantly and reversibly decreased (1) the amplitude, but not the shape of the compound action potential, (2) the amplitude and duration of the acetylcholine potential and (3) the residual fast excitatory postsynaptic potential recorded from neurons of the 9th and 10th paravertebral ganglia of the bullfrog Rana catesbeiana. The excitability of B-type ganglion neurons in the presence of nicotinic and muscarinic receptor antagonists was increased by compound 48/80 without altering the input resistance or membrane potential. In addition, compound 48/80 (10-50 micrograms/ml) significantly decreased the duration of the spike afterhyperpolarization (AHP). The amplitude but not the decay rate of the current underlying the slow component of the spike AHP was decreased by compound 48/80. Compound 48/80 did not, however, alter either the amplitude or the duration of calcium-dependent spikes. Intracellular recordings from dissociated sympathetic neurons also demonstrated a compound 48/80-induced increase in neuronal excitability. These results suggest that compound 48/80 interacts with the nicotinic receptor/channel complex to decrease ganglionic transmission, and also has a direct action to increase neuronal excitability by blocking potassium channels mediating the duration of the spike AHP.
authors.affiliation: Department of Anatomy and Neurobiology, University of Vermont, College of Medicine, Burlington 05405.
authors.forename: T J
authors.initials: TJ
authors.lastname: Heppner
authors.forename: J F
authors.initials: JF
authors.lastname: Fiekers
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D005725:Ganglia, Autonomic / Q000187:drug effects* / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018733:Nicotinic Antagonists; D011892:Rana catesbeiana; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D003189:p-Methoxy-N-methylphenethylamine; D000109:Acetylcholine; D002118:Calcium