The inhibitory effect of propranolol on ATP-sensitive potassium channels in neonatal rat heart

Abstract

1. Whole cell and single channel recordings of ATP-sensitive K⁺ current (I_K,ATP) were carried out in ventricular myocytes isolated from neonatal rat hearts.

2. (±)-Propranolol, a commonly used β-blocker, inhibited the whole cell I_K,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 (I_K,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 I_K,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 I_K,1 was also blocked by (±)-propranolol in the same way as I_K,ATP.

4. (+)-Propranolol, an optic isomer having no β-blocking effect, inhibited I_K,ATP (IC₅₀=5.8±1.0 μM), whilst atenolol, a selective β₁-blocker had no effect. Neither GDPβS (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 β-adrenergic signal transduction pathway, but by direct inhibition of I_K,ATP channels.

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