Inhibition of Ca2+ and K+ channels in sympathetic neurons by neuropeptides and other ganglionic transmitters.
Neuropeptides are known to modulate the excitability of frog sympathetic neurons by inhibiting the M-current and increasing the leak current, but their effects on Ca2+ channels are poorly understood. We compared effects of LHRH, substance P, epinephrine, and muscarine on Ca2+, K+, and leak currents in dissociated frog sympathetic neurons. At concentrations that inhibit M-current, LHRH and substance P strongly reduced N-type Ca2+ current and induced a leak conductance that may contribute to slow EPSPs. In contrast, muscarine produced little reduction of Ca2+ current, even in cells in which it strongly suppressed the M-current. We find that peptidergic inhibition of Ca2+ channels involves G proteins, but does not require protein kinases. In addition, it leads to reductions in Ca2(+)-activated K+ current and catecholamine release.
Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, Palo Alto, California 94305.
K R
KR
Bley
R W
RW
Tsien
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003891:Desipramine / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D004837:Epinephrine / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005728:Ganglia, Sympathetic / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D066298:In Vitro Techniques; D009116:Muscarine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011892:Rana catesbeiana; D011894:Rana pipiens; D013373:Substance P / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D015220:Calcium Channels; D015221:Potassium Channels; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D009116:Muscarine; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine