Computational Modeling of Neurons: Intensity-Duration Relationship of Extracellular Electrical Stimulation for Changes in Intracellular XXXX .

@entity16 @entity1372 @entity8425 @entity460 @entity972 @entity141 @entity528
UNASSIGNED: In many instances of extensive @entity16 , the injured nerve never adequately heals leaving lack of nerve function. @entity8425 ( @entity8425 ) has been shown to increase the rate and orient the direction of neurite growth, and is a promising therapy. However, the mechanism in which @entity8425 affects neuronal growth is not understood, making it difficult to compare existing @entity8425 protocols or to design and optimize new protocols. We hypothesize that @entity8425 acts by elevating intracellular @entity460 ([ @entity141 ]i) via opening voltage-dependent @entity141 channels (VDCCs). Here, we have created a computer model to estimate the @entity8425 @entity141 relationship. Using COMSOL Multiphysics, we modeled a small dorsal root ganglion (DRG) neuron that includes one @entity1372 , two @entity972 , and three VDCCs to estimate [ @entity141 ]i in the soma and growth cone. As expected, the results show that an @entity8425 that generates action potentials (APs) can efficiently raise the [ @entity141 ]i of neurons. More interestingly, our simulation results show that sub-AP @entity8425 can efficiently raise neuronal [ @entity141 ]i, and that specific high voltage @entity8425 can preferentially raise [ @entity141 ]i in the growth cone. The intensities and durations of @entity8425 on modeled growth cone @entity460 rise are consistent with directionality and orientation of growth cones experimentally shown by others. Finally, this model provides a basis to design experimental @entity8425 pulse parameters, including duration, intensity, pulse-train frequency, and pulse-train duration to efficiently raise [ @entity141 ]i in @entity528 or growth cones.
