PEPCK and Epilepsy

The physiological role of PEPCK in the brain has not been well studied.  Published literature shows that the enzyme is expressed at neuronal synapses, and radiolabeled metabolic studies suggest that there is significant enzymatic activity of PEPCK in the brain of well-nourished rats.  This page presents some work that I have done on the physiological role of PEPCK, especially how it relates to epilepsy and the ketogenic diet.
Background on PEPCK, the ketogenic diet as well as synaptic transmission can be found on other pages on this site.

To investigate the role of PEPCK in epilepsy, I used a model system that consists of slices of brain from the hippocampus of rats.  The hippocampus is very important in memory storage and retrieval and is the most studied area in the brain.  Many models of human epilepsy are made from the rat hippocampus, and the one I used is the high-potassium mode.  In this model system, rat brains are removed, and cut in to thin slices.  These slices can be kept alive by placing them in Artificial Cerebrospinal Fluid (ACSF) that is warmed and saturated with oxygen.  This keeps many of the neuronal electrical and biochemical properties intact.  Since hippocampal neurons are highly interconnected, hippocampal slices placed in a ACSF with elevated external potassium (7.5 mM Ko) will synchronize their electrical activity and fire action potentials in a co-coordinated manner.  These synchronized firing times are called a ‘burst’ and lasts approximately 100 ms, during which time each neuron may fire multiple action potentials.  One of the amazing properties of high-potassium induced bursting is its regularity.  Each slice will burst every 3 to 10 seconds, and if left undisturbed they will maintain their frequency for 6 hours or more.  Drugs or other manipulations that increase the speed of bursting are considered to be pro- convulsant, and compounds that reduce the frequency of bursting are considered to be anti-convulsant.  This synchronous activity can be recorded by an extracellular recording electrode that is placed in the CA3 region of the hippocampus.  All the data below come from hippocampal slices placed in 7.5 mM external potassium.

Figure 1         Figure 2        Figure 3       Figure 4       Figure 5
Copyright 2011 Steve Kriegler