Improved Model of Hyperpolarisation-activated Conductances (Ih) in Hippocampal CA1 Neurons
Neurones of the mammalian central nervous system display a diverse repertoire of voltage-dependent ion-permeable channels that are the basis of the spiking and integrative activity of these cells. Ih, a non-specific cationic conductance that is activated by hyperpolarisation, is critical for membrane oscillation and bursting, as well as modulating dendritic synaptic input. Abnormalities of this conductance have been associated with focal, generalized and inherited forms of epilepsy, and have been found in several neuron types, including hippocampal CA1 cells.
Most models of this current used for heuristic simulations are based on very simple two-state forms of the Hodgkin-Huxley equations. They generally do not incorporate the complex time- and voltage-dependence of Ih, nor the sensitivity to cyclic nucleotides. Additionally, variations in subunit composition are generally not considered. Disparate interpretations of the role of Ih in epileptogenesis may reflect the inadequacy of the models currently available.
Markov-chain models allow much more realistic and flexible description of these channels. Two to four state Markov models have been constructed, based reconstructed data sets, and incorporated into single and multi-compartment neuronal models. Differential equation forms prepared for the Scilab and NEURON simulation environments were able to produce better simulations of the time and voltage dependence of Ih recorded from CA1 neurons than previous descriptions. When incorporated into single and multi-compartment models, the new model was able to reproduce important modulatory effects of this conductance seen in vitro.
This new description should enable more accurate simulations of the complex rhythmic voltage oscillations of mammalian central neurons. More realistic models will allow better understanding of the non-linear dynamical processes underlying normal and pathological activity, especially epilepsy.