Neverisky Daniel L, Abbott Geoffrey W
Bioelectricity Laboratory, Department of Pharmacology, and Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, California, USA.
Bioelectricity Laboratory, Department of Pharmacology, and Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, California, USA
FASEB J. 2017 Jul;31(7):2828-2838. doi: 10.1096/fj.201601334R. Epub 2017 Mar 10.
Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability. KCNQ2/3 channel activity is augmented by phosphatidylinositol 4,5-bisphosphate (PIP), which is generated from -inositol, an osmolyte transported into cells by sodium-dependent -inositol transporters (SMITs). Here, we discovered that KCNQ2/3 channels isoform-specifically colocalize with SMIT1 and SMIT2 at sciatic nerve nodes of Ranvier and in axon initial segments, and form channel-transporter complexes and KCNQ2/3 coexpression protected SMIT1 activity from the otherwise inhibitory effects of cellular depolarization imposed by elevating extracellular [K], and KCNQ2 was required for potentiation of SMIT activity by -inositol preincubation. Cytoskeletal disruption, which speeds PIP dispersion, attenuated potentiation of KCNQ2/3 currents by SMIT1-mediated -inositol uptake, suggesting close channel-transporter juxtaposition ensures KCNQ2/3 exposure to locally high -inositol-derived PIP concentrations. Thus, KCNQ2/3-SMIT1/2 coassembly permits cross talk physical interaction, and may also be required for optimal, reciprocal indirect regulation membrane potential and PIP, especially within the specialized architecture of axons.-Neverisky, D. L., Abbott, G. W. KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk.
由KCNQ2和KCNQ3形成的电压门控钾通道对于正常神经元兴奋性至关重要。KCNQ2/3通道活性被磷脂酰肌醇4,5-二磷酸（PIP）增强，PIP由肌醇生成，肌醇是一种通过钠依赖性肌醇转运体（SMITs）转运进入细胞的渗透溶质。在这里，我们发现KCNQ2/3通道亚型特异性地与坐骨神经郎飞结处及轴突起始段的SMIT1和SMIT2共定位，并形成通道-转运体复合物，KCNQ2/3共表达保护SMIT1活性免受细胞外[K]升高所施加的细胞去极化的抑制作用，并且KCNQ2是肌醇预孵育增强SMIT活性所必需的。细胞骨架破坏会加速PIP扩散，减弱SMIT1介导的肌醇摄取对KCNQ2/3电流的增强作用，这表明通道-转运体紧密并列可确保KCNQ2/3暴露于局部高浓度的肌醇衍生的PIP中。因此，KCNQ2/3-SMIT1/2共组装允许相互作用——物理相互作用，并且可能也是最佳的相互间接调节膜电位和PIP所必需的，尤其是在轴突的特殊结构内。——涅韦尔斯基，D.L.，阿博特，G.W. KCNQ-SMIT复合物的形成促进离子通道-溶质转运体的相互作用。
