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)^1-3. Here we confirm the blocking effects of IAP and GTPγS (a nonhydrolysable analogue of GTP) on the ACh-induced Recurrent 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 GTPγS alone caused extremely slow, irreversible opening of K⁺-channels; however, repetitive receptor activations significantly increase the rate of the GTPγS effect. These results strongly suggest that a GTP-binding protein such as G_i regulates the opening of K ⁺-channels coupled with these receptors.