ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics.
The concentration dependence and kinetics of ionic currents activated by extracellular adenosine 5'-triphosphate (ATP) were studied in voltage-clamped dorsal root ganglion neurons from rats and bullfrogs. About 40% of neurons of both species responded to ATP with an increase in membrane conductance. The ATP-activated currents were similar in the 2 species, except that currents in rat neurons desensitized faster. In bullfrog neurons, the conductance was half-maximally activated by about 3 microM ATP; at low concentrations, the conductance increased 3- to 7-fold for a doubling in [ATP], suggesting that several ATP molecules must bind in order to activate the current. A steeper concentration-response relationship than expected from 1:1 binding was also seen in rat neurons. The current activated quickly upon application of ATP and decayed quickly when ATP was removed. Activation kinetics were faster at higher [ATP], with time constants decreasing from about 200 msec at 0.3 microM ATP to about 10 msec at 100 microM ATP. Deactivation kinetics (tau approximately 100-200 msec) were independent of the ATP concentration. The rapid activation and deactivation make it seem likely that the ATP-activated current is mediated by direct ligand binding rather than by a second-messenger system. The experimental observations can be mimicked by a simple model in which ATP must bind to 3 identical, noninteracting sites in order to activate a channel. The potency and kinetics of ATP action were voltage-dependent, with hyperpolarization slowing deactivation and increasing ATP's potency. Deactivation kinetics were also sensitive to the concentration of external Ca, becoming faster in higher Ca.
Bean
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Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009475:Neurons, Afferent / Q000378:metabolism*; D009994:Osmolar Concentration; D011892:Rana catesbeiana; D051381:Rats
D007473:Ion Channels; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D002118:Calcium