The new nanophysiology: regulation of ionic flow in neuronal subcompartments

Classical theories, such as cable theory, can only successfully model signal propagation in neurons on a macroscopic scale. Holcman and Yuste argue that, as the functional importance of neuronal compartments such as dendritic spines becomes apparent, it is important to develop models that can account for the effects of their size and geometry on electrical current flow. Cable theory and the Goldman–Hodgkin–Huxley–Katz models for the propagation of ions and voltage within a neuron have provided a theoretical foundation for electrophysiology and been responsible for many cornerstone advances in neuroscience. However, these theories break down when they are applied to small neuronal compartments, such as dendritic spines, synaptic terminals or small neuronal processes, because they assume spatial and ionic homogeneity. Here we discuss a broader theory that uses the Poisson–Nernst–Planck (PNP) approximation and electrodiffusion to more accurately model the constraints that neuronal nanostructures place on electrical current flow. This extension of traditional cable theory could advance our understanding of the physiology of neuronal nanocompartments.