Pertussis toxin and voltage dependence distinguish multiple pathways modulating calcium channels of rat sympathetic neurons.
Agonist-induced suppression of current in voltage-gated Ca2+ channels was studied in rat sympathetic neurons. We have previously distinguished two intracellular signaling pathways used by muscarinic agonists to suppress neuronal Ca2+ current-one fast and membrane delimited, the other slow and acting via a diffusible second messenger. We now show that the fast pathway is sensitive mainly to pertussis toxin and shifts the gating of Ca2+ channels to more positive voltages (voltage dependent). The slow pathway is pertussis toxin insensitive and depresses currents at all test potentials (voltage independent). Muscarinic agonists may also activate a pertussis toxin-insensitive fast pathway. alpha-Adrenergic agonists use the fast pertussis toxin-sensitive and the fast insensitive pathways, but not the slow one.
Beech
D J
DJ
Department of Physiology and Biophysics, University of Washington, Seattle 98195.
Bernheim
L
L
Hille
B
B
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D010095:Oxotremorine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine