Properties and pharmacological modification of ATP-sensitive K(+) channels in cat tracheal myocytes.
The effects of levcromakalim and nucleoside diphosphates (NDPs) on both membrane currents and unitary currents in cat trachea myocytes were investigated by use of patch-clamp techniques. In conventional whole-cell configuration, levcromakalim produced a concentration-dependent K(+) current which was suppressed by additional application of 5 microM glibenclamide at -70 mV. When 3 mM ATP was added in the pipette solution, the peak amplitude of the levcromakalim-induced current was much smaller than that in the absence of ATP. When 3 mM uridine 5'-diphosphate (UDP) was included in the pipette solution, much higher concentrations of glibenclamide (>/=50 microM) were required to suppress the 100 microM levcromakalim-induced membrane current in comparison with those in the absence of UDP. In the cell-attached patches, levcromakalim activated a 40 pS K(+) channel which was inhibited by additional application of glibenclamide in symmetrical 140 mM K(+) conditions. UDP (>/=0.1 mM) was capable of reactivating the channel in inside-out patches in which the glibenclamide-sensitive K(+) channel had run down, in the presence of levcromakalim. The K(+) channel reactivated by UDP was suppressed by additional application of either intracellular 3 mM ATP or 100 microM glibenclamide. These results demonstrate that smooth muscle cells in the cat trachea possess ATP-sensitive 40 pS K(+) channels which are blocked by glibenclamide (i.e. K(ATP)) and can be activated by levcromakalim and that intracellular UDP causes a significant shift of the glibenclamide-sensitivity of these channels.
Teramoto
N
N
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. noritera@linne.med.kyushu-u.ac.jp
Nakashima
T
T
Ito
Y
Y
D018528:ATP-Binding Cassette Transporters; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002415:Cats; D019806:Cromakalim / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D014530:Uridine Diphosphate / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D019806:Cromakalim; D006153:Guanosine Diphosphate; D014530:Uridine Diphosphate; D000244:Adenosine Diphosphate; D005905:Glyburide