A Mathematical Model of the Human Cardiac Na+ Channel

J Membr Biol. 2019 Feb;252(1):77-103. doi: 10.1007/s00232-018-00058-x. Epub 2019 Jan 14.

Abstract

Sodium ion channel is a membrane protein that plays an important role in excitable cells, as it is responsible for the initiation of action potentials. Understanding the electrical characteristics of sodium channels is essential in predicting their behavior under different physiological conditions. We investigated several Markov models for the human cardiac sodium channel NaV1.5 to derive a minimal mathematical model that describes the reported experimental data obtained using major voltage clamp protocols. We obtained simulation results for peak current-voltage relationships, the voltage dependence of normalized ion channel conductance, steady-state inactivation, activation and deactivation kinetics, fast and slow inactivation kinetics, and recovery from inactivation kinetics. Good agreement with the experimental data provides us with the mechanisms of the fast and slow inactivation of the human sodium channel and the coupling of its inactivation states to the closed and open states in the activation pathway.

Keywords: Inactivation; Ion channel gating; Markov model; NaV1.5 channel; Recovery from inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Electrophysiology
  • Humans
  • Ion Channel Gating*
  • Kinetics
  • Markov Chains
  • Models, Theoretical*
  • Myocardium / metabolism*
  • Protein Interaction Domains and Motifs
  • Structure-Activity Relationship
  • Voltage-Gated Sodium Channels / chemistry
  • Voltage-Gated Sodium Channels / metabolism*

Substances

  • Voltage-Gated Sodium Channels