Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 49 for “"Sodium channels"”.
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Slow Inactivation of Sodium Channels: Structural Clues and Disease Associations
Voltage gated sodium channels underlie the rapid upstroke of action potentials in electrically excitable mammalian tissues. A cardinal feature of Na+ channels is their ability to rapidly inactivate to a refractory state during membrane depolarization, in a process known as 'fast inactivation'. …
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Modeling of Electrostatic Interactions inside Human Voltage-Gated Sodium Channels
… permeation of Na+ through human voltage-gated sodium channels (Navs). Despite their biological significance, the selective permeation mechanism of Nav channels remains poorly understood at the molecular level. Here, we calculated electric fields inside the channel pore of Nav1.5, 1.6, and 1.7 …
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Kinetics of local anesthetic binding to sodium channels : role of pKa̳
Thesis (Ph. D.)--Harvard University--Massachusetts Institute of Technology Division of Health Sciences and Technology, Program in Medical Engineering and Medical Physics, 1989.
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Targeting protein: protein interaction sites for drug development against voltage-gated sodium channels
Voltage-gated sodium (Nav) channels are responsible for initiation and propagation of action potentials, which contribute to control of neuronal excitability. Malfunction of specific Nav channel isoforms is associated with a wide range of brain disorders including psychological, neurological and …
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Exploring mechanisms of inhibition and inactivation in voltage-gated sodium channels using molecular simulations
Voltage-gated sodium (Nav) channels play a pivotal role in the conduction of electrical signals across the human body, with different subtypes expressed across excitable tissue in the brain, heart and muscle. Nav channels transiently form transmembrane pores by cycling through the closed, open and …
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Exploring mechanisms of inhibition and inactivation in voltage-gated sodium channels using molecular simulations
Voltage-gated sodium (Nav) channels play a pivotal role in the conduction of electrical signals across the human body, with different subtypes expressed across excitable tissue in the brain, heart and muscle. Nav channels transiently form transmembrane pores by cycling through the closed, open and …
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Augmentations vs. Restoration: A computational study of the effects of bacterial sodium channels on cardiac conduction.
… Augmentation of cardiomyocytes with exogenous sodium channels such as Nav1.4 or prokaryotic voltage-gated sodium channels, or BacNavs, have shown promise for potentially alleviating these arrhythmias. However, due to size constraints, only the BacNavs are available for the highest efficiency …
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A single molecule study on the structural basis of ion selective permeation in voltage-gated sodium channels
High resolution studies of voltage-gated sodium channels (VGSCs) can not reveal the dynamic nature of the channel structures, especially in lipid environments, which are vital for rational drug design. The bacterial NavAb channel is highly like its eukaryotic orthologs in structure, function, and …
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Adaptive evolution, sex-linkage, and gene conversion in the voltage-gated sodium channels of toxic newts and their snake predators
… resistance through mutations in voltage-gated sodium channels, the protein targets of tetrodotoxin, sparking an evolutionary arms race between predator and prey. In this dissertation, I describe how genomic rearrangements have led to sex-linkage of four of the voltage-gated sodium channel genes …
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The Relationship between Ephaptic Coupling and Excitability in Ventricular Myocardium
… and subsequent recruitment of voltage gated sodium channels to trigger an action potential. Conduction in cardiomyocytes is dependent on the robustness and speed of action potential propagating through tissue. Both are equally important for normal heart function and claim to be linear …
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Mechanisms and plasticity of cold sensitivity in peripheral neurons
… receptor potential (TRP) family of cation channels are currently recognised as the principal transducers of thermal stimuli in sensory neurons, and two channels, TRPM8 and TRPA1, have been implicated in cold sensation. Ratiometric calcium imaging and quantitative rt-PCR studies revealed …
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Sex Differences in Cardiac Electrophysiology
… electrical communication rely on gap junctions, sodium channels and the perinexus. When conduction is disrupted it causes arrhythmias. When investigating these three critical determinants of cardiac conduction in guinea pig hearts, we determined that there are sex differences in two of three …
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Modulation of Axonal Transmission by Metabolic Stress
… modulate the DCMD axon’s performance and what channels are involved in high-frequency signaling that may be a target for metabolic stress. To investigate metabolic stress, we compared azide, a mitochondrial toxin, with starvation of 1- and 4-days. We found azide caused a similar reduction in …
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Characterization of the mechanisms behind the alternative splicing of the mutually exclusive exons 18N and 18A in the sodium channel gene SCN8A and mutually exclusive exons 5N and 5A in the soldium channel gene SCN9A
Voltage-gated sodium channels are the primary molecules responsible for the rising phase of action potentials in electrically excitable cells. There are 10 distinct sodium channel isoforms Na<sub>v</sub> 1.1-1.8 (SCNIA-SCN5A and SCN8A-SCNIIA) and the majority of these undergo tissue and …
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Optogenetic examination of salt taste in mice
… role in the detection and transduction of sodium taste via of epithelial sodium channels (ENaCs). Experiment 1 validated the function of a simple and affordable behavioral apparatus (hardware and software) for testing taste preference and taste aversion in mice. Experiment 2 demonstrated a …
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Effects of sodium chloride and sodium gluconate concentration on hydration behavior and water transport in the red-spotted toad, Bufo punctatus
… (3) transport of the chloride anion facilitates sodium uptake and affects sodium detection by the toad. The results of these studies also strongly suggest that general osmotic mechanisms as well as epithelial sodium channels function in chemosensation across the amphibian skin and that the …
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The Effects of Accessory Proteins on ENaC Function
… can lead to heart and kidney disease. Epithelial sodium channels, also known as ENaC, constitute the rate-limiting step of sodium reabsorption in the distal tubules of the nephron in the kidneys. It is here the final, yet critical, 3% to 5% of sodium reabsorption that dictates blood pressure …
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Structural and functional characterization of signaling protein complexes
… when bound to its substrates. All voltage-gated sodium channels possess the IQ motif for binding to calmodulin but are each differently regulated. Through biophysical and computational analyses, the mode of calmodulin binding to two high affinity sodium channel isoforms Nav1.4 and Nav1.6 was …
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