Suppression of 4-aminopyridine-induced paroxysmal depolarizing shift in rat amygdaloid neurons by diltiazem.

The effects of organic Ca2+ channel blocker, diltiazem, on the epileptiform activity induced by 4-aminopyridine (4-AP) were studied in rat amygdaloid slices using intracellular recording techniques. Application of 4-AP (0.5 mM) resulted in spontaneous and evoked epileptiform activity which consisted of an initial burst followed by a number of afterdischarges. The initial burst began with rapidly rising action potentials superimposed on a large depolarizing wave termed paroxysmal depolarizing shift (PDS). Diltiazem reversibly suppressed the amplitude and duration of PDS in a concentration-dependent manner. The IC50, estimated from the graph of the concentration-response relationship, was approximately 60 microM. These results demonstrate that a calcium current sensitive to diltiazem is involved in the generation of PDS and suggest that PDS is based on giant synaptic conductance as well as endogenous calcium currents.