Effect of membrane properties on skeletal muscle fiber excitability: a sensitivity analysis

In this study, the sensitivity of skeletal muscle fiber excitability to changes in temperature and a range of geometrical, electrical and ionic membrane properties was examined using model simulation. A mathematical model of the propagating muscle fiber action potential (AP) was used to simulate muscle fiber APs while changing individual muscle fiber parameters in isolation to examine how they affect muscle fiber AP amplitude, shape and conduction velocity (CV). The behavior of the model was verified by comparison with previously reported experimental data from both in vivo studies conducted at physiological temperatures and in vitro and in silico studies conducted at lower temperatures. The simulation results presented demonstrate the sensitivity of AP amplitude, shape and CV and, therefore, muscle fiber excitability to small changes in a wide range of different muscle fiber parameters. Furthermore, they demonstrate the potential of computational modeling as a tool for investigating the underlying mechanisms of complex phenomena such as those which govern skeletal muscle excitation.