The role of inositol trisphosphate on ACh-induced outward currents in bullfrog saccular hair cells.
Acetylcholine (ACh) is considered as the most likely candidate for a neurotransmitter of the efferent synapse onto hair cell. In this paper, the nature of this cholinergic receptor mechanism on dissociated bullfrog saccular hair cell was examined by using whole cell recording and Ca2+ sensitive fluorophotometric technique. Both the ACh-induced current and the increase of [Ca2+]i were observed in an oscillatory manner, and were the largest around the basal part of the cell where the efferent synapse is thought to make a contact with the membrane. The reversal potential of ACh-induced current indicated that ACh activated a K+ conductance. The ACh-induced current was reversibly blocked by atropine, d-tubocurarine (dTC), apamin, tetraethylammonium (TEA) and quinine. Neither muscarine nor nicotine mimicked the ACh-induced current. When GTP gamma S was injected into a hair cell, the first ACh application induced an outward current of transient kinetics, but in subsequent trials ACh-induced current lost its decay phase. Intracellularly injected D-myo-inositol 1,4,5-trisphosphate (InsP3) generated outward currents. Intracellularly injected heparin suppressed ACh-induced currents, and lithium (Li+) increased ACh-induced currents. These results indicate that ACh activates a receptor coupled with a guanine nucleotide binding protein (G-protein) which triggers metabolic cascades of InsP3 and Ca2+ leading to the activation of the Ca(2+)-activated K+ channel.
Yoshida
N
N
Department of Physiology, Faculty of Medicine, Kyoto University, Japan.
Shigemoto
T
T
Sugai
T
T
Ohmori
H
H
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D011892:Rana catesbeiana; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D010276:Parasympatholytics; D010277:Parasympathomimetics; D015221:Potassium Channels; C052455:nitr 5; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D008094:Lithium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium