Alpha-conotoxin-ImI: a competitive antagonist at alpha-bungarotoxin-sensitive neuronal nicotinic receptors in hippocampal neurons.
In the present study, the patch-clamp technique was applied to rat hippocampal neurons or myoballs in culture to study the actions of alpha-conotoxin-ImI on the native alpha-bungarotoxin-sensitive, presumably alpha 7-bearing, neuronal nicotinic receptor and on other ligand-gated channels. Preexposure of the neurons for 5 min to alpha-conotoxin-ImI decreased the peak amplitude of alpha-BGT-sensitive currents (referred to as type IA currents) in a concentration-dependent fashion. Several lines of evidence revealed that the inhibitory effect of alpha-conotoxin-ImI was competitive with respect to the agonist (IC50 approximately 85 nM) and reversible by washing. At 300 nM, alpha-conotoxin-ImI decreased by only 15% the peak amplitude of ACh-evoked currents in rat myoballs, did not affect the activation of currents gated by gamma-aminobutyric acid, glycine, N-methyl-D-aspartate, kainate, or quisqualate in hippocampal neurons, but reduced to approximately 60% the peak amplitude and shortened the decay phase of curare-sensitive, serotonin-gated currents in these neurons. The competitive and reversible nature of the alpha-conotoxin-ImI-induced inhibition of native alpha 7-bearing neuronal nicotinic receptors makes this peptide a valuable new tool for the functional and structural characterization of these receptors in the central nervous system.
Pereira
E F
EF
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, USA.
Alkondon
M
M
McIntosh
J M
JM
Albuquerque
E X
EX
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D020916:Conotoxins; D004553:Electric Conductivity; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology
D020916:Conotoxins; D018733:Nicotinic Antagonists; D009842:Oligopeptides; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; C087686:alpha-conotoxin ImI; D012701:Serotonin