Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon.
Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon.
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BK 通道 (KCa1.1) 在豚鼠远端结肠电动 K 分泌激活过程中的作用。
DOI：
10.1152/ajpgi.00325.2012
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Halm,DanR
中科院分区：
文献类型：
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作者：
Zhang,Jin;Halm,SusanT;Halm,DanR
分泌物作用于多种受体类型，激活豚鼠远端结肠电原性K+分泌，通常伴有Cl−分泌。不同的KCa1.1 (BK,Kcnma1), iberiotoxin （IbTx）和paxilline阻断剂抑制与K+分泌相关的负短路电流（Isc）。粘膜添加IbTx抑制肾上腺素激活的disc （epiIsc）和经上皮传导（epiGt），这与通过根尖膜KCa1.1分泌K+一致。抑制IbTx的浓度依赖性为193 nM，最大抑制率为51%。同样，IbTx抑制depigt， ic50为220 nM，最大抑制率为48%。粘膜添加paxilline （10 μM）抑制depiis5 - 50%。IbTx和paxilline也能抑制粘膜ATP的失活，支持顶端KCa1.1作为K+促分泌剂的需要。对IbTx和paxilline的反应表明，在前列腺素e2和胆碱能刺激激活Cl -分泌的过程中，K+分泌成分发生了变化。对远端结肠上皮细胞中KCa1.1α mRNA表达的分析表明，COOH末端存在zerosplice变体和三个剪接变体。还证实了调节β-亚基KCaβ1和KCaβ4的存在。免疫定位支持KCa1.1α在表面细胞和隐窝细胞的根尖和基底膜中的存在。综上所述，这些结果支持了电致K+分泌的细胞机制，在几种促分泌物类型的激活过程中，涉及根尖膜KCa1.1，但观察到的K+分泌可能需要根尖膜中其他K+通道类型的活性。
Secretagogues acting at a variety of receptor types activate electrogenic K+secretion in guinea pig distal colon, often accompanied by Cl−secretion. Distinct blockers of KCa1.1 (BK,Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (Isc) associated with K+secretion. Mucosal addition of IbTx inhibited epinephrine-activatedIsc(epiIsc) and transepithelial conductance (epiGt) consistent with K+secretion occurring via apical membrane KCa1.1. The concentration dependence of IbTx inhibition ofepiIscyielded an IC50of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibitedepiGtwith an IC50of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibitedepiIscandepiGtby ∼50%. IbTx and paxilline also inhibitedIscactivated by mucosal ATP, supporting apical KCa1.1 as a requirement for this K+secretagogue. Responses to IbTx and paxilline indicated that a component of K+secretion occurred during activation of Cl−secretion by prostaglandin-E2and cholinergic stimulation. Analysis of KCa1.1α mRNA expression in distal colonic epithelial cells indicated the presence of theZEROsplice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits KCaβ1 and KCaβ4 also was demonstrated. Immunolocalization supported the presence of KCa1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K+secretion involving apical membrane KCa1.1 during activation by several secretagogue types, but the observed K+secretion likely required the activity of additional K+channel types in the apical membrane.