1 Whole cell and single channel recordings of ATP-sensitive K. current (IK.ATP) were carried out in ventricular myocytes isolated from neonatal rat hearts. 2 (±)-Propranolol, a commonly used ß-blocker, inhibited the whole cell IK.ATP in a concentration-dependent manner with a half-maximal concentration (IC50) of 6.7 ± 1.4 μM, whereas it blocked the inward rectifier K† current (IK.1) only at much higher concentrations (IC50= 102.4 ± 20.2 μM). The inhibition was time- and voltage-independent. 3 In the outside-out patch configuration, ( ± )-propranolol inhibited IK.ATP (IC50= 9.8 ± 2.9 μM) by decreasing the open probability of the channel without inducing additional noise in the open-channel current or a decrease of single channel conductance. The single channel current of IK.1 was also blocked by ( ± )-propranolol in the same way as IK.ATP. 4 ( + )-Propranolol, an optic isomer having no ß-blocking effect, inhibited IK.ATP (IC50) = 5.8 ± 1.0 μM). whilst atenolol, a selective ß-blocker had no effect. Neither GDPßS (1 mM) nor GTPγS (200 μM) included in the pipette solution modulated the inhibitory effect of ( ± )-propranolol. 5 We concluded that the inhibitory effect of ( ± )-propranolol was not via the ß-adrenergic signal transduction pathway, but by direct inhibition of IK.AYP channels.
All Science Journal Classification (ASJC) codes
- ATP-sensitive K channel
- Patch clamp
- Rat heart