How the Nerve cell Excitability and Firing Properties Depend on the Density of Ion Channels in the Cell membrane
by
Peter Århem(Dept. of Neorophysiology, KI)
→
Europe/Stockholm
FA32
FA32
Description
It is now 60 years since Hodgkin in a classical study categorized the types of firing behaviour of crab axons. This study is still the basis for the analysis of firing patterns in nervous systems. He separated between two main classes of nerve cells; one being characterized by a discontinuous onset of firing with a non-zero frequency (about 20 Hz) at stimulation threshold (Type I), and the other by a continuous onset of firing (0 Hz; Type II) at threshold. This classification is applicable to mammalian cortical neurons, showing a class of neurons (mainly interneurons) with Type I characteristics (fast spiking neurons), and another (mainly pyramidal cells) with Type II characteristics (regular spiking neurons).
The underlying mechanisms of these behaviours are poorly understood, traditionally being assumed to depend on different mixtures of ions channels with varying kinetics. Our studies, comprising bifurcation analysis and computional modelling, suggest an alternative explanation. .
We show that many of the features of the two patterns (fast and regular
spiking) can be simulated in a neuron model by varying the number of channels per membrane area. Distinct oscillatory patterns, similar to those described in Hodgkin's study, are found to be associated with distinct regions in the sodium - potassium channel density plane. High sodium channel and low potassium channel densities cause the model to fire repetitively with very low frequencies (regular firing), while higher potassium channel densities cause the model to fire abruptly with non-zero frequency at stimulation threshold (fast spiking). A stability analysis shows that the different regions in the sodium-potassium channel density plane, and thus the different firing patterns, are mathematically characterized by saddle-node, Hopf and double-orbit bifurcations.
The study suggests novel scenarios for pharmacological regulation of neural activity. Certain anaesthetics might function by modifying frequency patterns and hence information processing and the level of consciousness, trough channel density regulation. Network modelling shows that these ideas are feasible.
