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 μM. 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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology