A single GTP-binding protein regulates K+-channels coupled with dopamine, histamine and acetylcholine receptors.
Recently, a GTP-binding protein sensitive to islet activating protein (IAP) has been suggested to be important in producing K+-currents when the muscarinic receptor of the atrial muscle is activated by acetylcholine (ACh). Here we confirm the blocking effects of IAP and GTP gamma S (a nonhydrolysable analogue of GTP) on the ACh-induced K+-current recorded from the ganglion cells of the sea slug Aplysia and compare their effects on histamine (HA)-induced and dopamine (DA)-induced K+-currents. Intracellular injections of IAP irreversibly and selectively block the openings of K+-channels activated by either ACh, HA, or DA without affecting the resting potential or conductance states of the membranes. Intracellular application of GTP gamma S alone caused extremely slow, irreversible opening of K+-channels; however, repetitive receptor activations significantly increase the rate of the GTP gamma S effect. These results strongly suggest that a GTP-binding protein such as Gi regulates the opening of K+-channels coupled with these receptors.
D000818:Animals; D001048:Aplysia; D002463:Cell Membrane Permeability; D003000:Clonidine / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007473:Ion Channels / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D007473:Ion Channels; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011968:Receptors, Histamine; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009020:Morphine; D006160:Guanosine Triphosphate; D012964:Sodium; D019204:GTP-Binding Proteins; D003000:Clonidine; D011188:Potassium