Article
Biology
Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne
Summary: The resurgent component of the voltage-gated sodium current (I-NaR) is a depolarizing conductance that regulates the firing properties of various neuronal cell types. The mechanism behind the generation of I-NaR, mediated by voltage-gated sodium channels, remains unclear. This study provides evidence that resurgent Na+ influx occurs as a result of fast inactivating Nav channels transitioning into an open/conducting state on membrane hyperpolarization, and the decay of I-NaR reflects the slow accumulation of recovered/opened Nav channels into a second inactivated state. The amplitude of I-NaR can be modulated by factors such as the accessory Nav beta 4 channel subunit.
Article
Food Science & Technology
Dana Katz, Dan Sindhikara, Michael DiMattia, Abba E. Leffler
Summary: By combining computational methods with experimental data, this study found that structure-based computational methods can effectively predict the potency changes of Gating modifier toxins (GMTs) mutants in inhibiting the sodium channel Na(V)1.7. The free-energy perturbation (FEP) method showed higher predictive accuracy compared to the widely used molecular mechanics/generalized born-surface area (MM-GB/SA) method, expanding the potential applications of computational approaches in biologics drug discovery programs.
Article
Cell Biology
Jiangtao Zhang, Shiqi Liu, Junping Fan, Rui Yan, Bo Huang, Feng Zhou, Tian Yuan, Jianke Gong, Zhu Huang, Daohua Jiang
Summary: In this study, cryoelectron microscopy was used to obtain structures of the Slo2.2 channel in closed, open, and inhibitor-bound form, providing insights into its cation regulation and inhibition. The closed state of Slo2.2 contains multiple K+ and Zn2+ binding sites in the cytoplasmic gating ring domain, which stabilize the closed conformation. The open state reveals Na+-sensitive sites that induce gating ring expansion and rotation upon Na+ binding, leading to inner gate opening. Additionally, a potent inhibitor blocks the pore by binding to a pocket formed by the pore helix and S6 helix. These findings establish a structural framework for studying Slo2.2 channel gating, Na+ sensation, and inhibition.
Article
Biochemistry & Molecular Biology
Guido Gessner, Mahdi Jamili, Pascal Tomczyk, Dirk Menche, Roland Schoenherr, Toshinori Hoshi, Stefan H. Heinemann
Summary: Hemin can potently inhibit the human cardiac voltage-gated sodium channel hNa(V)1.5, while being ineffective on other sodium channels. Its impact on hNa(V)1.5 channels is reversely use dependent, potentially modulating cardiac function by interacting with the voltage sensor of domain II.
BIOLOGICAL CHEMISTRY
(2022)
Article
Engineering, Chemical
Xi Zhang, Jiushuai Deng, Mingzhu Huangfu, Yu Wang, Bozeng Wu, Sihao Li, Zengrui Pang, Hui Mei
Summary: This study found that ferric ions can enhance the floatability of specularite by improving the chemical properties of the mineral surface and increasing the number of active sites.
Article
Biochemistry & Molecular Biology
M. Yu. Myshkin, A. S. Paramonov, D. S. Kulbatskii, E. A. Surkova, A. A. Berkut, A. A. Vassilevski, E. N. Lyukmanova, M. P. Kirpichnikov, Z. O. Shenkarev
Summary: Voltage-gated sodium channels have modular architecture with five membrane domains, where peripheral voltage-sensing domains are responsible for channel activation and rapid inactivation. Gating modifier toxins from arthropod venoms interact with these domains, potentially serving as prototypes for new drugs. In this study, the toxin Hm-3 showed high affinity to VSD-III of human skeletal muscle Na(V)1.4 channel, with specific residues likely interacting with the channel and the lipid bilayer.
Article
Pharmacology & Pharmacy
Arash Yavari, Mostafa Saffary, Ali Nokhodchi, Seyed Kazem Sadjady
Summary: This study investigates the impact of manufacturer variability of croscarmellose sodium (CCS), a superdisintegrant, on the dissolution of sitagliptin phosphate and escitalopram oxalate tablets. The physicochemical properties of CCS powders from four different manufacturers were studied, and it was found that there were differences in the swelling behavior of the CCS samples. Tablets with different concentrations of CCS were prepared, and it was observed that tablets with highly swelling CCS had superior dissolution profiles. The functional differences between CCSs produced by various manufacturers are affected by the drug solubility and the ratio of the disintegrant used in the formulations.
Article
Geochemistry & Geophysics
Pavlo Kryvenko, Igor Rudenko, Oleksandr Kovalchuk, Oleksandr Gelevera, Oleksandr Konstantynovskyi
Summary: This study investigates the effect of modifying admixtures on the structure formation and properties of alkali-activated slag cement. It was found that glycerol and trisodium phosphate, as components of a complex admixture, can control the setting of the cement and improve its physical and mechanical properties.
Article
Multidisciplinary Sciences
Elisabetta Mantuano, Pardis Azmoon, Michael A. Banki, Cory B. Gunner, Steven L. Gonias
Summary: In this study, we compared three ligands of LRP1 that inhibit inflammatory responses triggered by LPS. These ligands activate cell signaling and require N-methyl-D-aspartate receptor and intact lipid rafts. Among them, alpha M-2 is the only ligand that absolutely requires LRP1, while S-PrP can activate cell signaling independently of membrane-anchored PrPc.
SCIENTIFIC REPORTS
(2022)