Adenosine A(2) receptors are involved in the activation of ATP-sensitive K+ currents during metabolic inhibition in guinea pig ventricular myocytes

作者：Pan Sheng Jun^*; Li Li Rong

来源：Canadian Journal of Physiology and Pharmacology, 2011, 89(3): 187-196.

• ATP-sensitive potassium channel
• adenosine
• protein kinase C
• ischemic preconditioning
• cardiomyocytes

It has been hypothesized that an interaction among adenosine A(1) receptors, protein kinase C (PKC) activation, and ATP-sensitive potassium channels (K-ATP) mediates ischemic preconditioning in experiments on different animal species. The purpose of this study was to determine if activation of K-ATP is functionally coupled to A1 receptors and (or) PKC activation during metabolic inhibition (MI) in guinea pig ventricular myocytes. Perforated-patch using nystatin and conventional whole-cell recording methods were used to observe the effects of adenosine and adenosine-receptor antagonists on the activation of K-ATP currents during MI induced by application of 2,4-dinitrophenol (DNP) and 2-deoxyglucose (2DG) without glucose, in the presence or absence of a PKC activator, phorbol 12-myristate 13-acetate (PMA). Adenosine accelerated the time course activation of K-ATP currents during MI under the intact intracellular condition or dialyzed condition with l mmol/L ATP in the pipette solution. The accelerated effect of adenosine activation of K-ATP under MI was not reversed by a nonselective A(1) adenosine receptor antagonist, 8-(p-sulfophenyl) theophylline (SPT), or a specific A(1) adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). However, the adenosine A(2) receptor antagonist alloxazine reversed the time course activation of the K-ATP current under MI. An adenylate cyclase activator, forskolin, did not further abbreviate the time course activation of K-ATP with or without adenosine. Application of a PKC blocker, chelerythrine, reversed the time course activation of K-ATP by adenosine under MI. In addition, pretreatment with a PKC activator, PMA, had similar effects to adenosine, while adenosine did not further shorten the time required for activation of K-ATP currents during MI with PMA pretreatment. There is no direct evidence of activation of K-ATP currents by adenosine A(1) receptor during metabolic inhibition under our experimental condition. However, adenosine A(2) receptor activation is involved in the K-ATP channel activation in the guinea pig ventricular myocytes, of which effect is not mediated through the increase in intracellular cAMP. Adenosine seems to interact with PKC activation to open K-ATP during MI, but a possible link between the adenosine A(2) receptor and PKC activation in this process needs further elucidation.

• 出版日期2011-3
• 单位黄淮学院