Muscarine and t-LHRH suppress M-current by activating an IAP-insensitive G-protein.
The control of M-current by muscarinic ACh receptors and luteinizing hormone releasing hormone (LHRH) receptors was studied in dialyzed frog sympathetic ganglion neurons. M-current was recorded in dialyzed cells without run-down or changes in its biophysical properties and could be reversibly suppressed by muscarine and teleost LHRH (t-LHRH). However, dialysis with internal solutions lacking ATP or substituting with APP(NH)P caused the loss of M-current, suggesting that dephosphorylation suppresses the activity of M-channels. M-current over-recovers after agonist addition and removal to a size 30% larger than control, as if latent channels are activated during the recovery. Dialysis of cells with the G-protein activators GTP gamma S, fluoride, and aluminum fluoride causes loss of M-current. G-protein activation by receptors was confirmed by dialysis with low concentrations of GTP gamma S in competition with GTP. This prevents the rapid loss of M-current, but addition of muscarine or t-LHRH caused irreversible loss of M-current, suggesting that both transmitter receptors do suppress M-current by activating a G-protein. Suppression of M-current was not affected by treatment with 0.1 microgram/ml pertussis toxin (IAP) for 24-48 hr. In addition, based on the lack of IAP-specific labeling of frog sympathetic neuron membrane proteins, no IAP-sensitive G-proteins are present in these cells. These results indicate that an IAP-insensitive G-protein couples muscarinic and LHRH receptors to the suppression of M-current.
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D003956:Dialysis; D004351:Drug Resistance; D004553:Electric Conductivity; D005399:Fishes; D019204:GTP-Binding Proteins / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D009116:Muscarine / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D037342:Pertussis Toxin; D011894:Rana pipiens; D011976:Receptors, Muscarinic / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D006150:Guanine Nucleotides; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D007987:Gonadotropin-Releasing Hormone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009116:Muscarine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins