Department of Pharmacology and Toxicology, College of Veterinary Science & Animal Husbandry, Pandit Deen Dayal Upadhyaya Veterinary Sciences University & Cattle Research Institute, Mathura, India.
Anim Reprod Sci. 2011 Jul;126(3-4):173-8. doi: 10.1016/j.anireprosci.2011.05.014. Epub 2011 Jun 6.
Large conductance potassium channels (BK(Ca) channels) play a central role in maintaining myometrial tone, thus activation of these channels proved to have therapeutic potential in preterm labor. Present study aims to unravel the presence of BK(Ca) (maxi-K) channels in buffalo myometrium. Tension experiments, mRNA and protein expression studies were done to characterize BK(Ca) channels in buffalo myometrium. Isolated myometrial preparations exhibited rhythmic spontaneity with regular pattern of amplitude and frequency. Selective blockers of BK(Ca) channels iberiotoxin (IbTx; 100nM) and tetraethylammonium (TEA; 1mM) produced excitatory effects as evidenced by increase in amplitude and frequency of myogenic activity. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimi-dazol-2-one (NS-1619; 10(-7)-10(-4)M), a BK(Ca) channel opener, produced concentration-dependent relaxation of myometrium with pD(2) of 5.02±0.19 and R(max) of 31.35±3.5% (n=5). TEA significantly antagonized NS-1619-induced relaxation (pD(2) of 4.72±0.12 and R(max) of 22.72±1.78%; n=5). IbTx also significantly shifted the dose response curve of NS-1619 towards right (pD(2) of 3.98±0.16; n=4) without significant change in the per cent maximal response. Further, RT-PCR study detected mRNA encoding BK(Ca) α-subunit and Western blot analysis detected its protein expression in myometrium. Based on the results of the present investigation, it is suggested that BK(Ca) channels are present in the buffalo myometrium and are open in the resting state. Thus, their activation by potassium channel opener/β(2)-adrenoceptor agonist (tocolytic drug) may lead to uterine relaxation in preterm labor.
大电导钙激活钾通道（BK(Ca) 通道）在维持子宫肌紧张中起核心作用，因此这些通道的激活已被证明在早产中有治疗潜力。本研究旨在揭示水牛子宫肌中存在 BK(Ca)（大电导钾）通道。张力实验、mRNA 和蛋白质表达研究用于表征水牛子宫肌中的 BK(Ca) 通道。分离的子宫肌制备物表现出具有规则幅度和频率的节律自发性。BK(Ca) 通道的选择性阻断剂 Iberiotoxin（IbTx；100nM）和四乙基铵（TEA；1mM）产生兴奋作用，表现为肌原性活动幅度和频率增加。1,3-二氢-1-[2-羟基-5-(三氟甲基)苯基]-5-(三氟甲基)-2H-苯并咪唑-2-酮（NS-1619；10(-7)-10(-4)M），一种 BK(Ca) 通道开放剂，产生浓度依赖性的子宫肌松弛，pD(2)为 5.02±0.19，R(max)为 31.35±3.5%（n=5）。TEA 显著拮抗 NS-1619 诱导的松弛（pD(2)为 4.72±0.12，R(max)为 22.72±1.78%；n=5）。IbTx 也显著将 NS-1619 的剂量反应曲线向右移位（pD(2)为 3.98±0.16；n=4），而最大反应的百分比没有明显变化。此外，RT-PCR 研究检测到编码 BK(Ca)α亚基的 mRNA，Western blot 分析检测到其在子宫肌中的蛋白质表达。基于本研究的结果，建议 BK(Ca) 通道存在于水牛子宫肌中，在静息状态下是开放的。因此，它们被钾通道开放剂/β(2)-肾上腺素能受体激动剂（tocolytic 药物）激活可能导致早产时子宫松弛。
