Pharmacological characterization of the serotonin-sensitive potassium channel of Aplysia sensory neurons.
The effects of a variety of K+ channel blockers on current flow through single serotonin-sensitive K+ channels (the S channels) of Aplysia sensory neurons were studied using the patch-clamp technique. Tetraethylammonium (TEA), 4-aminopyridine (4-AP), and Co2+ and Ba2+ were first applied to the external membrane surface using cell-free outside-out patches. At concentrations up to 10 mM, these agents had little or no effect on single S-channel currents. At higher concentrations, external TEA acted as a fast open-channel blocker, reducing the single-channel current amplitude according to a simple one-to-one binding scheme with an apparent Kd of 90 mM. Blockage by external TEA is voltage independent. Internal TEA also acts as an open-channel blocker, with an apparent Kd of approximately 40 mM and a relatively weak voltage dependence, corresponding to an apparent electrical distance to the internal TEA-binding site of 0.1. Both internal and external TEA block the open channel selectively, with an affinity that is 10-100-fold greater than the affinity for the closed channel. Internal Ba2+ acts as a slow channel blocker, producing long closures of the channel, and binding with an apparent Kd of approximately 25-30 microM. These results show that single S-channel currents share a similar pharmacological profile with the macroscopic S current previously characterized with voltage clamp. On the basis of these results, a structural model for S-channel opening is proposed.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001048:Aplysia / Q000378:metabolism / Q000502:physiology*; D001464:Barium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D000631:Aminopyridines; D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D001464:Barium; D012701:Serotonin; D003035:Cobalt; D015761:4-Aminopyridine; D011188:Potassium