EFFECTS OF TOLBUTAMIDE ON ATP-SENSITIVE K+ CHANNELS FROM HUMAN RIGHT ATRIAL CARDIAC MYOCYTES

In order to gain further insight into possible deleterious effects on ischaemia-induced myocardial damage induced by sulfonylureas when admi nistered to humans, the effects of tolbutamide on ATP-sensitive K+ (K- ATP) channels from human right atrial myocytes were studied. Single my ocytes were enzymatically isolated from human right atrium. The cell-a ttached and inside-our configuration of the patch-clamp technique were employed at room temperature (both the pipette and the bath solution contained high [K+]). K-ATP channels in inside-out patches showed slig ht inward rectification, had a slope conductance of 75.1+/-2.4 pS (mea n+/-S.E.M.; n=5) at negative membrane potentials and these channels we re blocked by ATP (half-maximal block (EC(50)) at 39 mu M; Hill coeffi cient = 1.65). In cell-attached recordings, cromakalim (300 mu M) open ed K-ATP channels (with a slope conductance of 73.3+/-1.8 pS (n=16) at negative membrane potentials) in previously silent patches. Cromakali m-induced openings of K-ATP channels were not markedly affected by 100 or 300 mu M tolbutamide bur were blocked by tolbutamide at millimolar concentrations (1-3 mM). The concentration-response relationship for tolbutamide-induced block of K-ATP channels in the presence of 300 mu M cromakalim in cell-attached patches was calculated to values for the EC(50) of 1.325 mM and for the Hill coefficient of 1.0, respectively. 1 mM tolbutamide induced block of cromakalim-induced K-ATP channel op enings was not different at room temperature when compared to 37 degre es. It is concluded that K-ATP channels from human right atrial myocyt es have a low sensitivity towards tolbutamide-induced block.