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Synaptic impairment induced by paroxysmal ionic conditions in neocortex.

Publication Type:

Journal Article

Source:

Epilepsia, Volume 52, Issue 1, p.132-9 (2011)

Keywords:

Action Potentials, Animals, Animals, Newborn, Cats, Extracellular Space, Neocortex, Osmolar Concentration, Rats, Rats, Sprague-Dawley, Synapses

Abstract:

<p><b>PURPOSE: </b>Seizures are associated with a reduction in extracellular Ca²(+) concentration ([Ca²(+) ](o) ) and an increase in extracellular K(+) concentration ([K(+) ](o) ). The long-range synchrony observed between distant electrodes during seizures is weak. We hypothesized that changes in extracellular ionic conditions during seizures are sufficient to alter synaptic neuronal responses and synchrony in the neocortex.</p><p><b>METHODS: </b>  We obtained in vivo and in vitro electrophysiologic recordings combined with microstimulation from cat/rat neocortical neurons during seizures and seizure-like ionic conditions. In vitro the [K(+) ](o) was 2.8, 6.25, 8.0, and 12 mm and the [Ca²(+) ](o) was 1.2 and 0.6 mm.</p><p><b>KEY FINDINGS: </b>During seizures recorded in vivo, we observed abolition of evoked synaptic responses. In vitro, the membrane potential of both regular-spiking and fast-spiking neurons was depolarized in high [K(+) ](o) conditions and hyperpolarized in high [Ca²(+) ](o) conditions. During high [K(+) ](o) conditions, changes in [Ca²(+) ](o) did not affect membrane potential. The synaptic responsiveness of both regular-spiking and fast-spiking neurons was reduced during seizure-like ionic conditions. A reduction in [Ca²(+) ](o) to 0.6 mm increased failure rates but did not abolish responses. However, an increase in [K(+) ](o) to 12 mm abolished postsynaptic responses, which depended on a blockade in axonal spike propagation.</p><p><b>SIGNIFICANCE: </b>We conclude that concomitant changes in [K(+) ](o) and [Ca²(+) ](o) observed during seizures contribute largely to the alterations of synaptic neuronal responses and to the decrease in long-range synchrony during neocortical seizures.</p>

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