Imidazoline compounds inhibit KATP channels in guinea pig ventricular myocytes.
Phentolamine and related imidazolines inhibit KATP channel activity in the pancreatic beta cell. In the present study, the effects of several imidazoline-based compounds were examined upon KATP channel activity in guinea pig ventricular myocytes. Phentolamine produced a potent inhibition of KATP channel activity when examined in either excised inside-out patches or in the whole-cell configuration. This effect was unrelated to phentolamine's ability to antagonise alpha-adrenoceptors since the nonselective alpha-adrenoceptor antagonists, benextramine and phenoxybenzamine, failed to affect channel activity. Furthermore, the alpha-adrenoceptor agonist clonidine together with several related imidazolines inhibited channel activity. This suggests that imidazoline compounds modulate KATP channel activity in guinea pig ventricular myocytes and this may have clinical implications for the use of such agents as hypoglycemic drugs.
Lee
K
K
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201, USA.
Groh
W J
WJ
Blair
T A
TA
Maylie
J G
JG
Adelman
J P
JP
D000255:Adenosine Triphosphate / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D007093:Imidazoles; D015221:Potassium Channels; D000255:Adenosine Triphosphate