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Related Concept Videos

Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Ion Channels01:19

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...

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Markov models for ion channels: versatility versus identifiability and speed.

Martin Fink1, Denis Noble

  • 1Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK. martin.fink@dpag.ox.ac.uk

Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
|May 6, 2009
PubMed
Summary

Markov models (MMs) offer a flexible framework for ion channel modeling. This study addresses parameter estimation challenges, including unidentifiability and computational cost, proposing solutions for improved model development and validation.

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Area of Science:

  • Computational Biology
  • Biophysics
  • Mathematical Modeling

Background:

  • Markov models (MMs) generalize Hodgkin-Huxley models for diverse biological system dynamics.
  • Applications include single ion channel data, gating currents, and transporter function.
  • Cardiac electrophysiology serves as a key application domain for these models.

Purpose of the Study:

  • To investigate parameter estimation challenges in Markov models.
  • To address issues of parameter unidentifiability and computational expense.
  • To propose methods for enhancing the automation, validation, and predictive power of ion channel models.

Main Methods:

  • Analysis of parameter unidentifiability in 13 cardiac electrophysiology models.
  • Evaluation of experimental voltage step clamp data for information content.
  • Assessment of computational cost, focusing on model stiffness versus number of states.
  • Development of algorithms for steady-state analysis, analytical solutions, and parameter identifiability.

Main Results:

  • Parameter unidentifiability was found in 9 out of 13 models, hindering molecular insight.
  • A concise voltage step clamp protocol was identified as sufficient for parameter estimation.
  • Model stiffness, not the number of states, significantly impacts computation time.
  • Provided algorithms and software facilitate model analysis and identifiability assessment.

Conclusions:

  • Addressing parameter unidentifiability and computational cost is crucial for Markov model application.
  • Developed tools and protocols establish a new standard for automated ion channel model development.
  • Enhanced validation and predictive capabilities are enabled through improved modeling practices.