Quantification of gastrointestinal sodium channelopathy

Yong Cheng Poh, Arthur Beyder, Peter R. Strege, Gianrico Farrugia, Martin L. Buist

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Na v1.5 sodium channels, encoded by SCN5A, have been identified in human gastrointestinal interstitial cells of Cajal (ICC) and smooth muscle cells (SMC). A recent study found a novel, rare missense R76C mutation of the sodium channel interacting protein telethonin in a patient with primary intestinal pseudo-obstruction. The presence of a mutation in a patient with a motility disorder, however, does not automatically imply a cause-effect relationship between the two. Patch clamp experiments on HEK-293 cells previously established that the R76C mutation altered Na v1.5 channel function. Here the process through which these data were quantified to create stationary Markov state models of wild-type and R76C channel function is described. The resulting channel descriptions were included in whole cell ICC and SMC computational models and simulations were performed to assess the cellular effects of the R76C mutation. The simulated ICC slow wave was decreased in duration and the resting membrane potential in the SMC was depolarized. Thus, the R76C mutation was sufficient to alter ICC and SMC cell electrophysiology. However, the cause-effect relationship between R76C and intestinal pseudo-obstruction remains an open question.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalJournal of Theoretical Biology
StatePublished - Jan 21 2012


  • Computer model
  • Ion channel
  • Markov
  • Motility disorder
  • SCN5A

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics


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