IMIDAZOLINE COMPOUNDS INHIBIT K-ATP CHANNELS IN GUINEA-PIG VENTRICULAR MYOCYTES

Phentolamine and related imidazolines inhibit K-ATP channel activity in the pancreatic beta cell. In the present study, the effects of several imidazoline-based compounds were examined upon K-ATP channel activity in guinea pig ventricular myocytes. Phentolamine produced a potent inhibition of K-ATP 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 non-selective 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 K-ATP channel activity in guinea pig ventricular myocytes and this may have clinical implications for the use of such agents as hypoglycemic drugs.