  When neurons fire action potentials, dissipation of free energy is usually
not directly considered, because the change in free energy is often negligible
compared to the immense reservoir stored in neural transmembrane ion gradients
and the long-term energy requirements are met through chemical energy, i.e.,
metabolism. However, these gradients can temporarily nearly vanish in
neurological diseases, such as migraine and stroke, and in traumatic brain
injury from concussions to severe injuries. We study biophysical neuron models
based on the Hodgkin-Huxley (HH) formalism extended to include time-dependent
ion concentrations inside and outside the cell and metabolic energy-driven
pumps. We reveal the basic mechanism of a state of free energy-starvation (FES)
with bifurcation analyses showing that ion dynamics is for a large range of
pump rates bistable without contact to an ion bath. This is interpreted as a
threshold reduction of a new fundamental mechanism of 'ionic excitability' that
causes a long-lasting but transient FES as observed in pathological states. We
can in particular conclude that a coupling of extracellular ion concentrations
to a large glial-vascular bath can take a role as an inhibitory mechanism
crucial in ion homeostasis, while the Na$^+$/K$^+$ pumps alone are insufficient
to recover from FES. Our results provide the missing link between the HH
formalism and activator-inhibitor models that have been successfully used for
modeling migraine phenotypes, and therefore will allow us to validate the
hypothesis that migraine symptoms are explained by disturbed function in ion
channel subunits, Na$^+$/K$^+$ pumps, and other proteins that regulate ion
homeostasis.
