title: G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na+ channel interaction.
abstract: Our previous experiments in membranes prepared from rat heart and brain led us to suggest that the binding of agonists to the muscarinic receptors and to the Na+ channels is a coupled event mediated by guanine nucleotide binding protein(s) [G-protein(s)]. These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of [3H]acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of [3H]batrachotoxin to Na+ channel(s) in the presence of the muscarinic agonists; and (iii) muscarinically induced 22Na+ uptake in the presence and absence of tetrodotoxin, which blocks Na+ channels. Our findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na+ channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components--receptor, G-protein, and Na+ channel--is such that at resting potential the muscarinic receptor induces opening of Na+ channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000378:metabolism
chemical_list: D001496:Batrachotoxins; D007473:Ion Channels; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D013779:Tetrodotoxin; D012964:Sodium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine