Inactivating BK channels in rat chromaffin cells may arise from heteromultimeric assembly of distinct inactivation-competent and noninactivating subunits
Inactivating BK channels in rat chromaffin cells may arise from heteromultimeric assembly of distinct inactivation-competent and noninactivating subunits
复制标题
DOI：
10.1016/s0006-3495(98)77785-9
复制
发表时间：
1998-01-01
影响因子：
3.4
通讯作者：
Lingle, CJ
中科院分区：
文献类型：
--
作者：
Ding, JP;Li, ZW;Lingle, CJ
在大鼠染色质细胞中发现了大电导，Ca2+依赖性，电压依赖性bk型通道的失活和非失活变体，并且在很大程度上分离到不同的细胞中。在这里，我们验证了这样一个假设：在表达失活BK电流（BK，电流）的细胞群体中，BKi通道主要是由失活亚单位（BK (i)）和非失活亚单位（BK (s)）组成的异聚体。有几种独立的证据支持这一观点。胰蛋白酶逐渐消除失活与大多数细胞和斑块中平均每个通道约有两到三个失活结构域的想法是一致的。此外，白肉毒素（CTX）阻断BK电流的几个方面与BKi通道含有不同数量（至4个）相对CTX抗性的BK (i)亚基的观点一致。最后，在主要失活BKi通道的斑块中，非失活BKs通道的出现频率与两个不同亚基随机独立组装的二项预期一致，如果大多数细胞平均每个通道约有2至3个bk(i)亚基。这些结果表明，BKi电流的表型特性和由此产生的细胞电兴奋性可能表现出连续的行为，这仅仅是由两个不同亚基的差异表达引起的。
Inactivating and noninactivating variants of large-conductance, Ca2+-dependent, voltage-dependent BK-type channels are found in rat chromaffin cells and are largely segregated into different cells. Here we test the hypothesis that, within the population of cells that express inactivating BK current (BK, current), the BKi channels are largely heteromultimers composed of inactivation-competent subunits (bk(i)) and noninactivating subunits (bk(s)). Several independent types of evidence support this view. The gradual removal of inactivation by trypsin is consistent with the idea that in most cells and patches there are, on average, about two to three inactivation domains per channel. In addition, several aspects of blockade of BK, current by charybdotoxin (CTX) are consistent with the idea that BKi channels contain differing numbers tone to four) of relatively CTX-resistant bk(i) subunits. Finally, the frequency of occurrence of noninactivating BKs channels in patches with predominantly inactivating BKi channels is consistent with the binomial expectations of random, independent assembly of two distinct subunits, if most cells have, on average, about two to three bk(i) subunits per channel. These results suggest that the phenotypic properties of BKi currents and the resulting cellular electrical excitability may exhibit a continuum of behavior that arises simply from the differential expression of two distinct subunits.