Paper List
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EnzyCLIP: A Cross-Attention Dual Encoder Framework with Contrastive Learning for Predicting Enzyme Kinetic Constants
This paper addresses the core challenge of jointly predicting enzyme kinetic parameters (Kcat and Km) by modeling dynamic enzyme-substrate interaction...
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Tissue stress measurements with Bayesian Inversion Stress Microscopy
This paper addresses the core challenge of measuring absolute, tissue-scale mechanical stress without making assumptions about tissue rheology, which ...
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DeepFRI Demystified: Interpretability vs. Accuracy in AI Protein Function Prediction
This study addresses the critical gap between high predictive accuracy and biological interpretability in DeepFRI, revealing that the model often prio...
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Hierarchical Molecular Language Models (HMLMs)
This paper addresses the core challenge of accurately modeling context-dependent signaling, pathway cross-talk, and temporal dynamics across multiple ...
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Stability analysis of action potential generation using Markov models of voltage‑gated sodium channel isoforms
This work addresses the challenge of systematically characterizing how the high-dimensional parameter space of Markov models for different sodium chan...
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Personalized optimization of pediatric HD-tDCS for dose consistency and target engagement
This paper addresses the critical limitation of one-size-fits-all HD-tDCS protocols in pediatric populations by developing a personalized optimization...
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Consistent Synthetic Sequences Unlock Structural Diversity in Fully Atomistic De Novo Protein Design
This paper addresses the core pain point of low sequence-structure alignment in existing synthetic datasets (e.g., AFDB), which severely limits the pe...
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Generative design and validation of therapeutic peptides for glioblastoma based on a potential target ATP5A
This paper addresses the critical bottleneck in therapeutic peptide design: how to efficiently optimize lead peptides with geometric constraints while...
Stability analysis of action potential generation using Markov models of voltage‑gated sodium channel isoforms
School of Mathematics and Statistics, Rochester Institute of Technology | School of Physics, Rochester Institute of Technology | School of Physics and Astronomy & School of Mathematics and Statistics, Rochester Institute of Technology
The 30-Second View
IN SHORT: This work addresses the challenge of systematically characterizing how the high-dimensional parameter space of Markov models for different sodium channel isoforms influences the robustness and excitability of neuronal firing.
Innovation (TL;DR)
- Methodology Integrates a six-state Markov model for nine human NaV isoforms with a simplified KV3.1 model, enabling a unified framework for isoform-specific stability analysis.
- Methodology Applies bifurcation theory and local stability analysis to map 'excitable landscapes' across the (g_Na, g_K) parameter space, visualizing regions supporting stable oscillatory behavior.
- Biology Quantitatively ranks NaV isoforms by their supported excitable regimes, identifying NaV1.3, 1.4, and 1.6 as broadly supportive and NaV1.7 and 1.9 as minimally oscillatory.
Key conclusions
- Isoforms NaV1.3, NaV1.4, and NaV1.6 support the broadest parameter regions for stable limit cycles (oscillatory firing), indicating their robustness in sustaining action potential trains.
- Isoforms NaV1.7 and NaV1.9 exhibit minimal oscillatory behavior across the tested conductance parameter space, correlating with their specialized roles in peripheral nociception.
- The hybrid Markov-HH modeling and stability analysis framework successfully narrows the vast parameter search space for designing synthetic excitable systems, moving from trial-and-error to principled design.
Abstract: We investigate a conductance‑based neuron model to explore how voltage‑gated ion channel isoforms influence action‑potential generation. The model combines a six‑state Markov representation of NaV channels with a first‑order KV3.1 model, allowing us to vary maximal sodium and potassium conductances and compare nine NaV isoforms. Using bifurcation theory and local stability analysis, we map regions of stable limit cycles and visualize excitability landscapes via heatmap‑based diagrams. These analyses show that isoforms NaV1.3, NaV1.4 and NaV1.6 support broad excitable regimes, while isoforms NaV1.7 and NaV1.9 exhibit minimal oscillatory behavior. Our findings provide insights into the role of channel heterogeneity in neuronal dynamics and may help to guide the design of synthetic excitable systems by narrowing the parameter space needed for robust action‑potential trains.