This chapter describes the anti-epileptic effects of calcium channel blockade. The first sections deal with the underlying hypothesis and the experimental animal epilepsy models. Further sections describe the antiepileptic effects of organic calcium channel blockers in single neurons and in neuronal populations. The last section is devoted to control experiments showing the failure of effects of calcium channel blockers on non-epileptic neuronal activity.
The calcium mechanism underlying epileptic discharges
There are many observations that indicate that calcium ions are essentially involved in the generation of epileptic activity in the central nervous system (for reference, see Lux & Heinemann, 1983; Heinemann et al., 1986; Speckmann et al., 1986). At the level of single neurons, epileptic activity consists of a steep depolarization giving rise to a burst of action potentials, a plateau-like diminution of the membrane potential, and a steep repolarization that turns eventually into an afterdepolarization or an afterhyperpolarization (cf. Figs. 15.1–15.5)). This sequence of membrane potential changes has been described by Goldensohn & Purpura (1963), and called the paroxysmal depolarization shift (PDS) by Matsumoto & Ajmone Marsan (1964a,b).
Some landmarks leading to the ‘calcium concept’ of epileptic neuronal discharges are described in the following. First, the concentration of calcium ions in the extracellular space is diminished during seizure activity (Fig. 15.1 (a); Heinemann et al., 1977; Caspers et al., 1980; Heinemann & Louvel, 1983).