Effect of adenosine and intracellular GTP on KATP channels of mammalian skeletal muscle.
We investigated the action of adenosine and GTP on KATP channels, using inside-out patch clamp recordings from dissociated single fibers of rat flexor digitorum brevis (FDB) skeletal muscle. In excised patches, KATP channels could be activated by a combination of an extracellular adenosine agonist and intracellular Mg2+-ATP and GTP or GTP-gamma-S. The activation required hydrolyzable ATP and could be partially reversed with Mg2+, suggesting that it may involve a G-protein dependent phosphorylation of KATP channels. We found that KATP channels of the rat FDB could not be activated by Mg2+-ATP alone or by Mg2+-ATP in the presence of extracellular adenosine. Patches whose channel activity had been 'rundown' by Ca2+ could not be recovered by adenosine, GTP or Mg2+-ATP. KATP channels activated by adenosine receptor agonists had a similar ATP sensitivity to those under control conditions; but adenosine appears to be able to switch these KATP channels from an inactive to an active mode.
Barrett-Jolley
R
R
Ion Channel Group, Department of Cell Physiology & Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, UK.
Comtois
A
A
Davies
N W
NW
Stanfield
P R
PR
Standen
N B
NB
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects
D009124:Muscle Proteins; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D000266:Adenylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium