Convergence of multiple G-protein-coupled receptors onto a single type of potassium channel.
The light green cells (LGCs) in the central nervous system of the pond snail Lymnaea stagnalis form a homogeneous group of neuroendocrine cells that are involved in the control of growth and metabolism. These cells are inhibited by dopamine and the neuropeptides APGWamide, FMRFamide and GGSLFRFamide. Thus, the LGCs form an endogenous system in which processing and integration of different inputs into a physiological response can be studied. In this study we characterize the current(s) that are responsible for the inhibition of the LGCs by dopamine, APGWamide, FMRFamide and GGSLFRFamide. The responses are G-protein dependent, as follows from experiments with GTP-gamma-S. Several experiments indicate that the four agonists activate a single type of potassium channel. First, the currents evoked by the agonists have the same ion selectivity and voltage dependence. Potassium is the predominant charge carrier and the responses are weakly voltage sensitive, with conductance decreasing at potentials below approximately - 100 mV. Second, the currents activated by the four agonists display similar sensitivity towards several blockers. Internal and external TEA (10 mM), and extracellular Ba2+ (1 mM) cause a block of approximately 60-90%. External 4AP (1 mM) causes approximately 30% block and external Cs+ (1 mM) causes a voltage sensitive block. There is no sensitivity towards apamine and glibenclamide. Third, there is no summation of the responses to dopamine, APGWamide and GGSLFRFamide with maximal FMRFamide responses. Together, these data indicate that the responses induced by dopamine, APGWamide, FMRFamide and GGSLFRFamide are G-protein mediated and converge onto a single type of potassium channel in the LGCs of Lymnaea stagnalis.
van Tol-Steye
H
H
Department of Biochemistry and Molecular Biology, Research Institute Neurosciences, Vrije Universiteit, Amsterdam, The Netherlands.
Lodder
J C
JC
Planta
R J
RJ
van Heerikhuizen
H
H
Kits
K S
KS
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008195:Lymnaea / Q000502:physiology*; D009420:Nervous System / Q000166:cytology; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D015221:Potassium Channels; C063193:alanyl-prolyl-glycyl-tryptophanamide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019835:FMRFamide; D019204:GTP-Binding Proteins; D004298:Dopamine