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.
Gean
P W
PW
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Taiwan City, R.O.C.
Chou
S M
SM
D015761:4-Aminopyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D015761:4-Aminopyridine; D004110:Diltiazem