Fawcett Gloria L, Santi Celia M, Butler Alice, Harris Thanawath, Covarrubias Manuel, Salkoff Lawrence
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 2006 Oct 13;281(41):30725-35. doi: 10.1074/jbc.M605814200. Epub 2006 Aug 9.
Shal (Kv4) alpha-subunits are the most conserved among the family of voltage-gated potassium channels. Previous work has shown that the Shal potassium channel subfamily underlies the predominant fast transient outward current in Drosophila neurons (Tsunoda, S., and Salkoff, L. (1995) J. Neurosci. 15, 1741-1754) and the fast transient outward current in mouse heart muscle (Guo, W., Jung, W. E., Marionneau, C., Aimond, F., Xu, H., Yamada, K. A., Schwarz, T. L., Demolombe, S., and Nerbonne, J. M. (2005) Circ. Res. 97, 1342-1350). We show that Shal channels also play a role as the predominant transient outward current in Caenorhabditis elegans muscle. Green fluorescent protein promoter experiments also revealed SHL-1 expression in a subset of neurons as well as in C. elegans body wall muscle and in male-specific diagonal muscles. The shl-1 (ok1168) null mutant removed all fast transient outward current from muscle cells. SHL-1 currents strongly resembled Shal currents in other species except that they were active in a more depolarized voltage range. We also determined that the remaining delayed-rectifier current in cultured myocytes was carried by the Shaker ortholog SHK-1. In shl-1 (ok1168) mutants there was a significant compensatory increase in the SHK-1 current. Male shl-1 (ok1168) animals exhibited reduced mating efficiency resulting from an apparent difficulty in locating the hermaphrodite vulva. SHL-1 channels are apparently important in fine-tuning complex behaviors, such as mating, that play a crucial role in the survival and propagation of the species.
Shal(Kv4)α亚基在电压门控钾通道家族中是最保守的。先前的研究表明,Shal钾通道亚家族是果蝇神经元中主要的快速瞬态外向电流(Tsunoda, S., and Salkoff, L. (1995) J. Neurosci. 15, 1741 - 1754)以及小鼠心肌中快速瞬态外向电流的基础(Guo, W., Jung, W. E., Marionneau, C., Aimond, F., Xu, H., Yamada, K. A., Schwarz, T. L., Demolombe, S., and Nerbonne, J. M. (2005) Circ. Res. 97, 1342 - 1350)。我们发现,Shal通道在秀丽隐杆线虫肌肉中作为主要的瞬态外向电流也发挥着作用。绿色荧光蛋白启动子实验还揭示了SHL - 1在一部分神经元以及秀丽隐杆线虫体壁肌肉和雄性特异性对角肌中的表达。shl - 1(ok1168)无效突变体消除了肌肉细胞中的所有快速瞬态外向电流。SHL - 1电流与其他物种中的Shal电流非常相似,只是它们在更去极化的电压范围内具有活性。我们还确定,培养的心肌细胞中剩余的延迟整流电流是由Shaker直系同源物SHK - 1携带的。在shl - 1(ok1168)突变体中,SHK - 1电流有显著的代偿性增加。雄性shl - 1(ok1168)动物的交配效率降低,这是由于在定位雌雄同体的阴门时明显困难所致。SHL - 1通道显然在微调复杂行为(如交配)中很重要,而交配在物种的生存和繁殖中起着关键作用。