Pinacidil opens ATP-dependent K+ channels in cardiac myocytes in an ATP- and temperature-dependent manner.
Pinacidil is an antihypertensive agent that has been found to increase potassium conductance. This study examined the type of K channel affected by pinacidil in cardiac myocytes. Pinacidil shortened the action potential duration in papillary muscle. The effect was reversible upon addition of glyburide, a known IKATP blocker. The effect of pinacidil was temperature-dependent. Action potential duration was shortened more rapidly and to a greater extent at 37 degrees C than at 23 degrees C. Whole-cell experiments showed that I-V curves lost rectification after pinacidil treatment. As with the action potential experiments, the effect was more rapid at 37 degrees C than at 23 degrees C. Rectification was restored after exposure to glyburide. The I-V curve generated after pinacidil exposure was similar to that observed by others after treatment with metabolic inhibitors that activate IKATP. The effect of pinacidil was also ATP-dependent. Addition of 5 mM ATP to the internal solution prevented activation of IKATP. These data indicate that pinacidil activates IKATP.
Martin
C L
CL
Cardiovascular Disease Research, G.D. Searle & Co., Research and Development, Skokie, Illinois 60077.
Chinn
K
K
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature
D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide; D004121:Dimethyl Sulfoxide