U-37883A potently inhibits dopamine-modulated K+ channels on rat striatal neurons.
An 85 pS K+ channel of rat caudate-putamen neurons, which is activated by dopamine D2 receptors and inhibited by sulfonylurea drugs, was studied using cell-attached patch-clamp electrophysiology. This channel was inhibited by externally-applied U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl hydrochloride), a blocker of vascular ATP-sensitive K+ channels, with a half-maximal effect at a concentration of approximately 0.1 microM. Channel inhibition occurred in a time-dependent fashion when U-37883A was applied to the membrane from a back-filled patch pipette. Inhibition was associated with a decrease in fractional open time, but was voltage-insensitive and did not alter channel conductance, suggesting an effect on channel gating at a site largely insensitive to the electrical field of the channel. U-37883A was about 50 times more potent at inhibiting this channel than was the sulfonylurea drug glibenclamide. This relative potency, opposite to that found in pancreatic tissue, indicates that U-37883A is a useful tool to distinguish amongst different subtypes of sulfonylurea-sensitive K+ channels.
Lin
Y J
YJ
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Chen
X
X
Freedman
J E
JE
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats
D009025:Morpholines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C082658:U 37883A; D000218:Adamantane; D004298:Dopamine