The potassium channel opener cromakalim (BRL 34915) activates ATP-dependent K+ channels in isolated cardiac myocytes

Effects of cromakalim on the membrane potassium permeability of frog skeletal muscle in vitro

“…potent in smooth muscle where the EC50 for the increase in 86Rb efflux is around 1 JM (Quast & Cook, 1989). In cardiac muscle the EC50 is in the range 5-30 JM (Osterrieder, 1988;Escande et al, 1988;Sanguinetti et al, 1988) whilst in insulin-secreting cells cromakalim is relatively ineffective (Garrino et al, 1989;Dunne et al, 1990). Our results in frog skeletal muscle, like those of Spuler et al (1989) in human muscle suggest a potency between those in cardiac muscle and insulin-secreting cells.…”

“…glibenclamide) (Quast & Cook, 1989) which appear to be selective inhibitors of adenosine 5'-triphosphate (ATP)-sensitive K+ (KATP) channels (Sturgess et al, 1985;Ashcroft, 1988) it has been proposed that the actions of cromakalim are on this type of channel. Cromakalim has indeed now been shown to activate identified KATP channels in excised membrane patches of ventricular myocytes (Escande et al, 1988) and the important requirement for this hypothesis that smooth muscle possesses KATP channels has now been demonstrated (Standen et al, 1989;Kajioka et al, 1991).…”

Alkali cation permeability and caesium blockade of cromakalim‐activated current in guinea‐pig ventricular myocytes

“…A relatively small outward K + current is also evident at positive potentials (see below) and inward Na+ and Ca2+ currents inactivate rapidly and make little contribution to whole-cell current measured at the end of 100-200 ms voltage steps. described here, outward current measured at +80 mV in the presence of 100puM cromakalim (a concentration that induces an effect 80% of maximal) was 4.4 + 0.5 nA (range 1.5-12.5 nA, 31 cells) while under control conditions it was 0.65 + 0.03 nA, in good agreement with previous reports (Escande et al, 1988;Sanguinetti et al, 1988 Figure 2b). …”

“…Cromakalim is a benzopyran derivative that activates ATPsensitive K+ [K(ATP)] channels in cardiac myocytes (Escande et al, 1988;Sanguinetti et al, 1988), arterial smooth muscle cells (Standen et al, 1989) and an insulin-secreting cell line (Dunne et al, 1989). Since the relaxation of smooth muscle and decrease of blood pressure that it induces are inhibited by sulphonylureas such as glibenclamide (Standen et al, 1989;Quast & Cook, 1989a;Winquist et al, 1989;Cavero et al, 1989;Eltze, 1989) which block K(ATP) channels (SchmidAntomarchi et al, 1987;Sturgess et al, 1988), K(ATP) channel activation may be the primary mechanism of action of cromakalim.…”

Blockade by antiarrhythmic drugs of glibenclamide‐sensitive K+ channels in Xenopus oocytes

“…While the ATP-sensitive K+ channel is inactivated by an increase in intracellular ATP, it is activated by K+ channel openers such as cromakalim and pinacidil (Escande et al, 1988) and inactivated by antidiabetic sulphonylureas such as glibenclamide and tolbutamide (Sturgess et al, 1985).…”