Seizure-like afterdischarges simulated in a model neuron
To explore non-synaptic mechanisms in paroxysmal discharges, we used a computer model of a simplified hippocampal pyramidal cell, surrounded by interstitial space and a glial-endothelial buffer system. Ion channels for Na+, K+, Ca2+ and Cl? , ion antiport 3Na/Ca, and active ion pumps were represented in the neuron membrane. The glia had leak conductances and an ion pump. Fluxes, concentration changes and cell swelling were computed. The neuron was stimulated by injecting current. Afterdischarge (AD) followed stimulation if depolarization due to rising interstitial K+ concentration ([K+]o) activated persistent Na+ current (I Na,P). AD was either simple or self-regenerating; either regular (tonic) or burst-type (clonic); and always self-limiting. Self-regenerating AD required sufficient I Na,P to ensure re-excitation. Burst firing depended on activation of dendritic Ca2+ currents and Ca-dependent K+ current. Varying glial buffer function influenced [K+]o accumulation and afterdischarge duration. Variations in Na+ and K+ currents influenced the threshold and the duration of AD. The data show that high [K+]o and intrinsic membrane currents can produce the feedback of self-regenerating afterdischarges without synaptic input. The simulated discharge resembles neuron behavior during paroxysmal firing in living brain tissue.
ion channels epilepsy persistent current ion distribution potassium concentration firing pattern