Publications by authors named "Elaine Tao"
Small molecule inhibitors of the sodium channel are common pharmacological agents used to treat a variety of cardiac and nervous system pathologies. They act on the channel via binding within the pore to directly block the sodium conduction pathway and/or modulate the channel to favor a non-conductive state. Despite their abundant clinical use, we lack specific knowledge of their protein-drug interactions and the subtle variations between different compound structures.
View Article and Find Full Text PDFArticle Synopsis
- SCN2A gene-related early-infantile developmental and epileptic encephalopathy (EI-DEE) is a serious rare disorder caused by mutations affecting the Nav1.2 sodium channel, leading to abnormal neuronal activity in infants.
- The study examined seven specific mutations of the Nav1.2 channel, using techniques like molecular dynamics and electrophysiology, to understand how these mutations impact fast inactivation of the channel.
- Notably, the N1662D mutation severely hinders fast inactivation, highlighting the importance of interactions between amino acids N1662 and Q1494, while other mutations showed varying effects on channel function, including some that enhanced neuronal excitability.
Voltage-gated sodium channels (Naᵥ) are membrane proteins which open to facilitate the inward flux of sodium ions into excitable cells. In response to stimuli, Naᵥ channels transition from the resting, closed state to an open, conductive state, before rapidly inactivating. Dysregulation of this functional cycle due to mutations causes diseases including epilepsy, pain conditions, and cardiac disorders, making Naᵥ channels a significant pharmacological target.
View Article and Find Full Text PDFArticle Synopsis
- The 59-residue DI linker peptide in the hSkMNaV1.4 ion channel was absent in a CryoEM structure, but its unique sequence in mammalian skeletal muscle sodium channels suggests potential physiological and evolutionary significance.
- A homology model of the hSkMNaV1.4 channel revealed that the linker adopts a compact structure rather than being a random flexible coil, with sequence analysis showing high variability among 48 mammalian species.
- Investigations into conserved residues and a specific asparagine for N-linked glycosylation indicate it may interact with the DIV voltage sensing domain, influencing channel gating and linking the unique sequence and structure to its function.
Article Synopsis
- * Recent studies have revealed four fenestrations in the Nav pore module that affect how pore blockers access these channels, but differences in the fenestration sizes among the different subtypes are still not well understood.
- * Using molecular dynamics simulations, researchers found variability in the sizes of these fenestrations across Nav subtypes and identified specific residues that influence their dimensions, paving the way for future experiments on drug access related to sodium channel mutations and drug design.