Effects of adenosine receptor stimulation on guinea pig cardiac myocytes

已知内源性腺苷调节生理性心肌细胞功能，并在缺血和再灌注期间发挥保护作用。为了探索腺苷类似物作为心肌治疗剂的有效性，我们首先在全细胞膜片钳配置中检测腺苷对豚鼠心肌细胞的电生理作用。腺苷可缩短心房肌细胞动作电位时程（APD），使静息膜电位超极化，但对心室肌细胞无影响。当心房细胞与百日咳毒素（百日咳毒素）预孵育时，腺苷不缩短APD，证实腺苷受体。与IAP敏感的GTP结合蛋白偶联。在尼卡地平（一种L-型Ca^2+通道阻滞剂）存在下，腺苷增加0 mV的外向膜电流，这表明腺苷引起了特异性K^+外向电流。腺苷A_1受体激动剂，N^6-环己基腺苷（CHA），但不是A_2或A_3受体激动剂， ...更多信息 使腺苷引起的心房肌细胞动作电位时程缩短和膜电流增加。A_1受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX）可完全阻断上述作用。KATP通道阻断剂格列苯脲（Glybenclamide）可完全阻断CHA对APR的缩短作用，并部分阻断CHA对外向膜电流的影响，提示CHA的作用是通过激活质膜上的K通道而实现<ATP>的。此外，CHA对细胞外向膜电流的影响可被蛋白激酶C抑制剂白屈菜红碱（chelerythrine）完全阻断，并被线粒体钾通道特异性抑制剂5-羟基癸酸（5-HD）部分抑制<ATP>。结果提示，腺苷A_1受体激动引起的APD缩短，部分是通过<ATP>蛋白激酶C和5-HD敏感的细胞内信号通路激活钾通道而实现的，这可能参与腺苷对缺血再灌注损伤的保护作用。少

Endogenous adenosine is known to regulate the physiological cardiomyocyte function and to exert a protective action during ischemia and reperfusion. To explore the usefulness of adenosine analogue as a myocardial therapeutic agent, we first examined the electrophysiological effects of adenosine on guinea pig cardiomyocytes in the whole cell patch-clamp configuration. Adenosine shortened the action potential duration (APD) and hyperpolarized the resting membrane potential of atrial but not ventricular myocytes. When atrial cells were preincubated with pertussis toxin (LAP), adenosine did not shorten the APD, confirming that adenosine receptors. couple to the IAP-sensitive GTP-binding protein. Adenosine increased the outward membrane current at 0mV in the presence of nicardipine, an L-type Ca^<2+> channel blocker, which suggests that adenosine elicited the specific K^+-outward current. Adenosine A_1 receptor agonist, N^6-cyclohexyladenosine (CHA), but not A_2 or A_3 receptor agonist, rep … More roduced both the adenosine-induced shortening effect on APD and the increasing effect on the outward membrane current of atrial myocytes. These effects were completely abolished by A_1 receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). Glybenclamide, a KATP channel blocker, completely abolished the CHA-induced shortening effect on APR and also partially abolished the effect on the outward membrane current, which suggests that the effects of CHA are mediated by the activation of K_<ATP> channels on the plasma membrane. Further, the effect of CHA effect, on the outward membrane current was completely abolished by preincubating the cells with chelerythrine, a protein kinase C inhibitor, and was partially,inhibited by 5-hydroxydecanoic acid (5-HD), known as a specific inhibitor of mitochondrial K_<ATP> channels. These results suggest that the shortening of APD caused by adenosine A_1 receptor stimulation was conducted in part through an activation of K_<ATP> channels via protein kinase C and 5-HD-sensitive intracellular signaling pathways, which may be involved in the mechanisms by which adenosine exerts a protective action during ischemia and reperfusion. Less