The voltage-gated potassium (Kv) channel Kv1.5 mediates the IKur repolarizing current in human atrial myocytes and regulates vascular tone in multiple peripheral vascular beds. Understanding the complex regulation of Kv1.5 function is of substantial interest because it represents a promising pharmacological target for the treatment of atrial fibrillation and hypoxic pulmonary hypertension. Herein we demonstrate that posttranslational modification of Kv1.5 by small ubiquitin-like modifier (SUMO) proteins modulates Kv1.5 function. We have identified two membrane-proximal and highly conserved cytoplasmic sequences in Kv1.5 that conform to established SUMO modification sites in transcription factors. We find that Kv1.5 interacts specifically with the SUMO-conjugating enzyme Ubc9 and is a target for modification by SUMO-1, -2, and -3 in vivo. In addition, purified recombinant Kv1.5 serves as a substrate in a minimal in vitro reconstituted SUMOylation reaction. The SUMO-specific proteases SENP2 and Ulp1 efficiently deconjugate SUMO from Kv1.5 in vivo and in vitro, and disruption of the two identified target motifs results in a loss of the major SUMOconjugated forms of Kv1.5. In whole-cell patch-clamp electrophysiological studies, loss of Kv1.5 SUMOylation, by either disruption of the conjugation sites or expression of the SUMO protease SENP2, leads to a selective Ϸ15-mV hyperpolarizing shift in the voltage dependence of steady-state inactivation. Reversible control of voltage-sensitive channels through SUMOylation constitutes a unique and likely widespread mechanism for adaptive tuning of the electrical excitability of cells.electrical excitability ͉ posttranslational modification ͉ transmembrane protein ͉ ubiquitin-like modifier
The basic idea of H2-C mixture reduction reflexes using hydrogen as main reductor and carbon as main heat generator in iron bath smelt reduction reactors on purpose to cut down total energy consumption and CO2 emission. The author applied the methods of modeling for separating regions and [1]complex integration to research the kinetics behavior of the reactor. Changes of temperature and concentration field in each region were calculated after modeling from theories for solid-liquid, solid-gas and gas-liquid reactions combining theories of shrinking core, combustion and deoxidization etc. Besides some boundary- and initial conditions were got from inlet variables, other conditions included substance and energy exchanges on boundaries between different reaction regions were determined from the translation of all boundary coordination. After dispersion treatment with Control-Volume-Method, the whole model was programmed into special software for digital simulation. Corresponding author: HONG Xin, Shanghai University, Phone/Fax: 021-56331176, E-mail: xhong@online.sh.cn
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