Strength-duration relationship for intra- versus extracellular stimulation with microelectrodes

Chronaxie, a historically introduced excitability time parameter for electrical stimulation, has been assumed to be closely related to the time constant of the cell membrane. Therefore, it is perplexing that significantly larger chronaxies have been found for intracellular than for extracellular stimulation. Using compartmental model analysis, this controversy is explained on the basis that extracellular stimulation also generates hyperpolarized regions of the cell membrane hindering a steady excitation as seen in the intracellular case. The largest inside/outside chronaxie ratio for microelectrode stimulation is found in close vicinity of the cell. In the case of monophasic cathodic stimulation, the length of the primarily excited zone which is situated between the hyperpolarized regions increases with electrode-cell distance. For distant electrodes this results in an excitation process comparable to the temporal behavior of intracellular stimulation. Chronaxie also varies along the neural axis, being small for electrode positions at the nodes of Ranvier and axon initial segment and larger at the soma and dendrites. As spike initiation site can change for short and long pulses, in some cases strength-duration curves have a bimodal shape, and thus, they deviate from a classical monotonic curve as described by the formulas of Lapicque or Weiss.