Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity.
Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity.
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DOI：
10.1085/jgp.201411253
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Lingle CJ
中科院分区：
文献类型：
--
作者：
Martinez-Espinosa PL;Yang C;Gonzalez-Perez V;Xia XM;Lingle CJ
缺乏BKβ2亚单位的小鼠嗜铬细胞在电流注射过程中动作电位放电减少，但自发爆发放电增加。大鼠和小鼠肾上腺髓质嗜铬细胞(CCS)表达失活的BK电流。这种失活被认为是由多达四个β2辅助亚基(由kcnmb2基因编码)与形成孔的slo1α亚基的四聚体组装而成的。尽管失活的生理后果尚不清楚，但已有研究表明，不同CC之间去极化诱发的放电差异是由于β2亚单位改变BK通道激活范围的能力所致。为了研究含有β2亚单位的BK通道的作用，我们建立了编码β2基因缺失的小鼠(β2基因敲除[KO])。通过比较野生型(WT)和β2KO小鼠的蛋白质，可以明确地证明β2亚基在不同组织中的存在，以及它与slo1α亚基的共同组装。我们在脑片上比较了WT和β2 KO CCS的电流特性和细胞放电特性，发现β2 KO消除了失活，减缓了动作电位(AP)的复极，并在恒流注射过程中减少了AP的放电。这些结果支持β-2介导的BK通道激活范围的移动影响重复放电和AP特性的观点。出乎意料的是，β2 KO小鼠的CCS表现出自发放电的增加趋势，这表明在缺乏β2亚单位的情况下，BK通道的特殊性质可能易于发生猝发放电。
Chromaffin cells from mice lacking the BK β2 subunit show decreased action potential firing during current injection but an increase in spontaneous burst firing. Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four β2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 α subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of β2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing β2 subunits, we generated mice in which the gene encoding β2 was deleted (β2 knockout [KO]). Comparison of proteins from wild-type (WT) and β2 KO mice allowed unambiguous demonstration of the presence of β2 subunit in various tissues and its coassembly with the Slo1 α subunit. We compared current properties and cell firing properties of WT and β2 KO CCs in slices and found that β2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the β2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from β2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of β2 subunits may predispose to burst firing.
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