A5007973390- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Analytical Chemistry and Sensors
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- Electron and X-Ray Spectroscopy Techniques
- Advanced biosensing and bioanalysis techniques
- ATP Synthase and ATPases Research
- Molecular Sensors and Ion Detection
- Electrochemical Analysis and Applications
- Machine Learning in Materials Science
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Nicotinic Acetylcholine Receptors Study
- RNA Interference and Gene Delivery
- Insect and Pesticide Research
University of Rochester Medical Center
2020-2024
University of Rochester
2020-2023
Acid-sensing ion channels (ASICs) are neuronal sodium-selective activated by reductions in extracellular pH. Structures of the three presumptive functional states, high-pH resting, low-pH desensitized, and toxin-stabilized open, have all been solved for chicken ASIC1. These structures, along with prior data, suggest that isomerization or flipping β11–12 linker extracellular, ligand-binding domain is an integral component desensitization process. To test this, we combined fast perfusion...
Abstract Objective Gain‐of‐function variants in the KCNT1 gene, which encodes a sodium‐activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep‐related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression genetic mouse model by reducing Kcnt1 transcript divalent small interfering RNA (siRNA), an emerging variant...
Abstract Acid‐sensing ion channels (ASICs) are important players in detecting extracellular acidification throughout the brain and body. ASICs have large domains containing two regions replete with acidic residues: pocket, palm domain. In resting state, pocket is an expanded conformation but collapses low pH conditions as side chains neutralized. Thus, has been hypothesized to collapse that, turn, ultimately drives channel activation. However, several observations run counter this idea. To...
Desensitization is a common feature of ligand-gated ion channels, although the molecular cause varies widely between channel types. Mutations that greatly reduce or nearly abolish desensitization have been described for many including glutamate, GABA, glycine, and nicotinic receptors, but not acid-sensing channels (ASICs) until recently. Mutating Gln276 to glycine (Q276G) in human ASIC1a was reported mostly at both macroscopic single levels, potentially providing valuable tool subsequent...
Structures of the trimeric acid-sensing ion channel have been solved in resting, toxin-bound open and desensitized states. Within extracellular domain, there is little difference between state state. The main exception that a loop connecting 11th 12th β-strand, just two amino acid residues long, undergoes significant functionally critical re-orientation or flipping conformations. Here we investigate how specific interactions within surrounding area influence linker stability “flipped” using...
Abstract Desensitization is a common feature of ligand-gated ion channels although the molecular cause varies widely between channel types. Mutations that substantially reduce or abolish desensitization have been described for many including glutamate, GABA, glycine and nicotinic receptors but not acid-sensing (ASICs) until recently. Mutating Gln276 to in human ASIC1a was reported mostly at both macroscopic single levels, potentially providing valuable tool subsequent studies. However, we...
Abstract Acid-sensing ion channels (ASICs) are neuronal sodium-selective activated by reductions in extracellular pH. Structures of the three presumptive functional states, high-pH resting, low-pH desensitized, and toxin-stabilized open, have all been solved for chicken ASIC1. These structures, along with prior data, suggest that isomerization or flipping β11-12 linker extracellular, ligand-binding domain is an integral component desensitization process. To test this, we combined fast...