The inhibitory effect of propranolol on ATP-sensitive potassium channels in neonatal rat heart.
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 beta-blocker, inhibited the whole cell I(K,ATP) in a concentration-dependent manner with a half-maximal concentration (IC50) of 6.7 +/- 1.4 microM, whereas it blocked the inward rectifier K+ current (I(K,I)) only at much higher concentrations (IC50 = 102.4 +/- 20.2 microM). The inhibition was time- and voltage-independent. 3. In the outside-out patch configuration, (+/-)-propranolol inhibited I(K,ATP) (IC50 = 9.8 +/- 2.9 microM) 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,I) was also blocked by (+/-)-propranolol in the same way as I(K,ATP). 4. (+)-Propranolol, an optic isomer having no beta-blocking effect, inhibited I(K,ATP) (IC50 = 5.8 +/- 1.0 microM), whilst atenolol, a selective beta1-blocker had no effect. Neither GDPbetaS (1 mM) nor GTPgammaS (200 microM) included in the pipette solution modulated the inhibitory effect of (+/-)-propranolol. 5. We concluded that the inhibitory effect of (+/-)-propranolol was not via the beta-adrenergic signal transduction pathway, but by direct inhibition of I(K,ATP) channels.
Xie
L H
LH
Department of Physiology, Faculty of Medicine, Kyoto University, Japan.
Takano
M
M
Noma
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D019204:GTP-Binding Proteins / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D000255:Adenosine Triphosphate; D011433:Propranolol; D019204:GTP-Binding Proteins