A principal feature of a cardiomyocyte is its excitability, and the ion channels are fundamental to that respect, in particular:
     a) the sodium channel, which is responsible for the upstroke of the action potential
     b) the calcium channel, which triggers the intracellular calcium increase that will activate contraction
     c) the potassium channel, which will mediate the normalization of the membrane potential.

     Ion channels have been studied for over 40 years using voltage clamp and patch clump techniques to determine their characteristics i.e. current, voltage, time.

     It all started with the Hodgkin and Huxley nerve model, modelling three currents i.e. INa, I­K, IL(Physiological Laboratory, University of Cambridge, 1952). Alan L. Hodgkin and Andrew F. Huxley shared with Sir John Eccles the Nobel Prize in Physiology or Medicine in 1963.

     A suggested reference for their work is the following study,

Hodgkin, A. L. and A. F. Huxley (1952). "A quantitative description of membrane current and its application to conduction and excitation in nerve." J Physiol 117(4): 500-544

which is commented in a recent brief note by A.F. Huxley.

     A bibliographical reference for this classic model which has stood the test of time can be found at this link.

     The model exists in SBML in Biomodels, in CellML in the CellML repository and in the Virtual Heart.


     An example of a Markov or multistate model of the cardiac sodium channel is the study by Clancy, C. E. and Y. Rudy (1999). "Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia." Nature 400(6744): 566-569 which models the wild-type and a mutant form of the sodium channel (ΔKPQ). 

     After the two molecular models (wild-type and mutant) were formulated they were incorporated into a cellular model, an electrophysiology model, the Luo–Rudy dynamic cardiac cell model for action potential simulations (which is briefly mentioned in the cell modelling section).

     The simulation showed that the mutation of the sodium channel was responsible for a persistent sodium current during the action potential plateau. This defect was causing prolongation of repolarization and development of arrhytmogenic early afterdepolarizations. This behavior was consistent with the clinical phenotype of the patients that were carrying ths mutation.

     The study by Clancy, C. E. and Y. Rudy (2002). "Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism." Circulation 105(10): 1208-1213, presents a Markov model of another sodium channel mutation (1795insD) which is responsible for two arrythmia syndromes.

     The model is available in SBML in Biomodels and in CellML at the CellML repository.