SENSITIVITY ANALYSIS OF A MODEL OF MAMMALIAN NEURAL MEMBRANE

The sensitivity of the strength-duration (S-D) relationship to changes in the parameters describing the sodium channel of mammalian neuronal membrane was determined by computer simulation. A space-clamped patch of neuronal membrane was modeled by a parallel nonlinear sodium condu ctance, linear leakage conductance, and membrane capacitance. Each par ameter that governs the activation (m) and inactivation (h) variables of the sodium channel was,varied from -50% to + 50% of its default val ue, and for each variation a S-D relationship was generated. Individua l changes in six of the eleven parameters (alpha(m)A, alpha(m)D, alpha (h)A, beta(m)A, beta(m)B, and beta(h)B) generated substantial changes in the rheobase current and chronaxie time (Tch) of the model. Changin g the parameter values individually did not correct for the model's fa ilure to generate excitation after the release from a long duration hy perpolarization (anode break excitation). Scaling a combination of fiv e parameters (alpha(m)A, alpha(m)B, alpha(h)A, beta(m)A, and beta(h)B) by an equal amount produced a model that generated anode break excita tion and increased Tch, but also decreased the amplitude of the action potential. To reproduce the amplitude of the action potential, the ma ximum sodium conductance and sodium Nernst potential were increased. T hese modifications generated a model that had S-D properties closer to experimental results, could produce anode break excitation, and repro duced the action potential amplitude.