PDF(Pubmed)
Abstract：
Large-conductance Ca2+- and voltage-dependent potassium (BK) channels exhibit functional diversity not explained by known splice variants of the single Slo alpha-subunit. Here we describe an accessory subunit (beta3) with homology to other beta-subunits of BK channels that confers inactivation when it is coexpressed with Slo. Message encoding the beta3 subunit is found in rat insulinoma tumor (RINm5f) cells and adrenal chromaffin cells, both of which express inactivating BK channels. Channels resulting from coexpression of Slo alpha and beta3 subunits exhibit properties characteristic of native inactivating BK channels. Inactivation involves multiple cytosolic, trypsin-sensitive domains. The time constant of inactivation reaches a limiting value approximately 25-30 msec at Ca2+ of 10 microM and positive activation potentials. Unlike Shaker N-terminal inactivation, but like native inactivating BK channels, a cytosolic channel blocker does not compete with the native inactivation process. Finally, the beta3 subunit confers a reduced sensitivity to charybdotoxin, as seen with native inactivating BK channels. Inactivation arises from the N terminal of the beta3 subunit. Removal of the beta3 N terminal (33 amino acids) abolishes inactivation, whereas the addition of the beta3 N terminal onto the beta1 subunit confers inactivation. The beta3 subunit shares with the beta1 subunit an ability to shift the range of voltages over which channels are activated at a given Ca2+. Thus, the beta-subunit family of BK channels regulates a number of critical aspects of BK channel phenotype, including inactivation and apparent Ca2+ sensitivity.
摘要：
大电导Ca2和电压依赖性钾（BK）通道表现出功能多样性，而单个Sloα亚基的已知剪接变体无法解释。在这里，我们描述了与BK通道的其他β亚基具有同源性的辅助亚基（β3），当它与Slo共表达时赋予失活。在大鼠胰岛素瘤肿瘤（RINm5f）细胞和肾上腺嗜铬细胞中发现了编码β3亚基的信息，两者都表示BK通道失活。由Sloα和β3亚基共表达产生的通道表现出天然失活BK通道的特性。灭活涉及多个细胞溶质，胰蛋白酶敏感域。在10μM的Ca2和正激活电位下，失活的时间常数达到约25-30毫秒的极限值。与振动筛N端失活不同，但是就像原生灭活BK通道一样，胞质通道阻断剂不与天然失活过程竞争。最后,beta3亚基赋予对炭毒素的敏感性降低，如本地失活BK通道所见。失活产生于β3亚基的N末端。去除β3N末端（33个氨基酸）消除失活，而在beta1亚基上添加beta3N末端会导致失活。β3亚基与β1亚基具有改变电压范围的能力，在给定的Ca2下激活通道。因此，BK通道的β亚基家族调节BK通道表型的许多关键方面，包括失活和明显的Ca2+敏感性。
