Low levels of KATP channel activation decrease excitability and contractility of urinary bladder
Low levels of KATP channel activation decrease excitability and contractility of urinary bladder
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DOI：
10.1152/ajpregu.2001.280.5.r1427
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发表时间：
2001-05-01
影响因子：
2.8
通讯作者：
Nelson, MT
中科院分区：
文献类型：
--
作者：
Petkov, GV;Heppner, TJ;Nelson, MT
ATP 敏感钾 (K-ATP) 通道的激活可以通过膜电位超极化调节平滑肌功能。了解 K-ATP 通道作用的一个关键问题是通道激活与对组织功能的影响之间的关系。在这里，我们通过使用合成化合物 N-(4-苯甲酰基苯基)-3,3,3-三氟-2-羟基-2-甲基丙酰胺 (ZD-6169) 和 levcromakalim 激活 K-ATP 通道，探索了逼尿肌膀胱平滑肌 (UBSM) 中的这种关系。检查了 ZD-6169 和 levcromakalim 对分离的 UBSM 细胞中 K-ATP 通道电流、动作电位以及分离的 UBSM 条带的相关相位收缩的影响。 1.02和2.63μM的ZD-6169和levcromakalim分别引起单个UBSM细胞中K-ATP电流的半最大激活(K-1/2)(参见Heppner TJ、Bonev A、Li JH、Kau ST和Nelson MT.Pharmacology 53:170-179, 1996)。相比之下，低得多的浓度（ZD-6169 的 K-1/2 = 47 nM，levcromakalim 的 K-1/2 = 38 nM）引起动作电位和 UBSM 阶段性收缩的抑制。结果表明，激活
Activation of ATP-sensitive potassium (K-ATP) channels can regulate smooth muscle function through membrane potential hyperpolarization. A critical issue in understanding the role of K-ATP channels is the relationship between channel activation and the effect on tissue function. Here, we explored this relationship in urinary bladder smooth muscle (UBSM) from the detrusor by activating K-ATP channels with the synthetic compounds N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZD-6169) and levcromakalim. The effects of ZD-6169 and levcromakalim on K-ATP channel currents in isolated UBSM cells, on action potentials, and on related phasic contractions of isolated UBSM strips were examined. ZD-6169 and levcromakalim at 1.02 and 2.63 muM, respectively, caused half-maximal activation (K-1/2) of K-ATP currents in single UBSM cells (see Heppner TJ, Bonev A, Li JH, Kau ST, and Nelson MT. Pharmacology 53: 170-179, 1996). In contrast, much lower concentrations (K-1/2 = 47 nM for ZD-6169 and K-1/2 = 38 nM for levcromakalim) caused inhibition of action potentials and phasic contractions of UBSM. The results suggest that activation of