Wallner M, Meera P, Toro L
Department of Anesthesiology, University of California, Los Angeles, CA 90095-1778, USA.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4137-42. doi: 10.1073/pnas.96.7.4137.
Voltage-dependent and calcium-sensitive K+ (MaxiK) channels are key regulators of neuronal excitability, secretion, and vascular tone because of their ability to sense transmembrane voltage and intracellular Ca2+. In most tissues, their stimulation results in a noninactivating hyperpolarizing K+ current that reduces excitability. In addition to noninactivating MaxiK currents, an inactivating MaxiK channel phenotype is found in cells like chromaffin cells and hippocampal neurons. The molecular determinants underlying inactivating MaxiK channels remain unknown. Herein, we report a transmembrane beta subunit (beta2) that yields inactivating MaxiK currents on coexpression with the pore-forming alpha subunit of MaxiK channels. Intracellular application of trypsin as well as deletion of 19 N-terminal amino acids of the beta2 subunit abolished inactivation of the alpha subunit. Conversely, fusion of these N-terminal amino acids to the noninactivating smooth muscle beta1 subunit leads to an inactivating phenotype of MaxiK channels. Furthermore, addition of a synthetic N-terminal peptide of the beta2 subunit causes inactivation of the MaxiK channel alpha subunit by occluding its K+-conducting pore resembling the inactivation caused by the "ball" peptide in voltage-dependent K+ channels. Thus, the inactivating phenotype of MaxiK channels in native tissues can result from the association with different beta subunits.
电压依赖性和钙敏感性钾通道（大电导钾通道）是神经元兴奋性、分泌及血管张力的关键调节因子，因为它们能够感知跨膜电压和细胞内钙离子。在大多数组织中，对其进行刺激会产生一种非失活的超极化钾电流，从而降低兴奋性。除了非失活的大电导钾电流外，在嗜铬细胞和海马神经元等细胞中还发现了一种失活的大电导钾通道表型。失活的大电导钾通道的分子决定因素尚不清楚。在此，我们报道了一种跨膜β亚基（β2），它与大电导钾通道的孔形成α亚基共表达时会产生失活的大电导钾电流。细胞内应用胰蛋白酶以及缺失β2亚基的19个N端氨基酸会消除α亚基的失活。相反，将这些N端氨基酸与非失活的平滑肌β1亚基融合会导致大电导钾通道出现失活表型。此外，添加β2亚基的合成N端肽会通过堵塞其钾离子传导孔导致大电导钾通道α亚基失活，这类似于电压依赖性钾通道中“球”状肽引起的失活。因此，天然组织中大电导钾通道的失活表型可能是由与不同β亚基的结合导致的。
