Aromatic aldehydes and aromatic ketones open ATP-sensitive K+ channels in guinea-pig ventricular myocytes.
Patch-clamp techniques were used to study the effects of three carbonyl compounds, 3,4-dihydroxybenzaldehyde, 2,3-dihydroxybenzaldehyde, and 2,4-dihydroxyacetophenone, on the adenosine-5'-triphosphate(ATP)-sensitive K+ channel current (IK.ATP) in guinea-pig ventricular myocytes. 3,4-Dihydroxybenzaldehyde (0.5-1 mM) shortened the action potential duration, and this effect was inhibited by application of a specific blocker of IK.ATP, glibenclamide. The shortening of the action potential duration was shown to be caused by a time-independent outward current. In the cell-attached patch configuration, all three compounds activated a kind of single-channel current, which showed an inward rectification at positive potentials and which had a linear current/voltage relation at negative potentials, having a conductance of 90 pS. The current reversed at about 0 mV in symmetrical K+ concentrations on both sides of the membrane. In excised patches this current was blocked by internal application of ATP. Thus we identified this channel as IK.ATP. The activation effects of two aromatic aldehydes were stronger than that of the aromatic ketone. The effect of these compounds on IK.ATP was not reduced by addition of cysteine (10 mM). In inside-out patches, 3,4-dihydroxybenzaldehyde increased the activity of IK.ATP, which had been blocked by 0.5 mM MgATP in the presence of 0.5 mM ADP, but the activation effect was variable and much weaker than that in the cell-attached configuration, and was completely eliminated in the absence of ADP.(ABSTRACT TRUNCATED AT 250 WORDS)
Fan
Z
Z
Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Nakayama
K
K
Sawanobori
T
T
Hiraoka
M
M
D000098:Acetophenones / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001547:Benzaldehydes / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D000098:Acetophenones; D000447:Aldehydes; D000925:Anticoagulants; D001547:Benzaldehydes; D002396:Catechols; D007659:Ketones; D015221:Potassium Channels; C067077:2,3-dihydroxybenzaldehyde; C005581:protocatechualdehyde; C078634:2,4-dihydroxyacetophenone; D000255:Adenosine Triphosphate