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 administered to humans, the effects of tolbutamide on ATP-sensitive K+ (KATP) channels from human right atrial myocytes were studied. Single myocytes were enzymatically isolated from human right atrium. The cell-attached and inside-out configuration of the patch-clamp technique were employed at room temperature (both the pipette and the bath solution contained high [K+]). KATP channels in inside-out patches showed slight inward rectification, had a slope conductance of 75.1 +/- 2.4 pS (mean +/- S.E.M.; n = 5) at negative membrane potentials and these channels were blocked by ATP (half-maximal block (EC50) at 39 microM; Hill coefficient = 1.65). In cell-attached recordings, cromakalim (300 microM) opened KATP channels (with a slope conductance of 73.3 +/- 1.8 pS (n = 16) at negative membrane potentials) in previously silent patches. Cromakalim-induced openings of KATP channels were not markedly affected by 100 or 300 microM tolbutamide but were blocked by tolbutamide at millimolar concentrations (1-3 mM). The concentration-response relationship for tolbutamide-induced block of KATP channels in the presence of 300 microM cromakalim in cell-attached patches was calculated to values for the EC50 of 1.325 mM and for the Hill coefficient of 1.0, respectively. 1 mM tolbutamide-induced block of cromakalim-induced KATP channel openings was not different at room temperature when compared to 37 degrees. It is concluded that KATP channels from human right atrial myocytes have a low sensitivity towards tolbutamide-induced block.
Zünkler
B J
BJ
Federal Institute for Drugs and Medical Devices, Berlin, Germany.
Henning
B
B
Ott
T
T
Hildebrandt
A G
AG
Fleck
E
E
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D016280:Atrial Function, Right / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D002648:Child; D019806:Cromakalim; D004347:Drug Interactions; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D012680:Sensitivity and Specificity; D014044:Tolbutamide / Q000494:pharmacology*
D001578:Benzopyrans; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate; D014044:Tolbutamide