Effects of apamin and nicotinic acetylcholine receptor antagonists on inferior collicular seizures.
These studies compared the actions of apamin and nicotinic acetylcholine antagonists on seizure genesis within the inferior collicular cortex. In vitro alpha-bungarotoxin, d-tubocurarine and gallamine all competitively displaced [125I]apamin binding to brain sections through the inferior colliculus, while intracollicular microinjection of intermediate doses of apamin (21 pmol), alpha-bungarotoxin (0.3 nmol), d-tubocurarine (0.22 nmol) or gallamine (1.7 nmol) all significantly reduced the seizure initiation threshold current. However, higher doses of apamin did not cause spontaneous seizure activity, while higher doses of the nicotinic acetylcholine antagonists caused spontaneous seizures. Carbamylcholine also produced spontaneous seizures, but did not alter the seizure threshold current. N-Methyl-atropine caused a dose-related elevation of the seizure threshold current, yet microinjection of N-methyl-atropine (10 nmol) into the inferior collicular cortex reversed the effects of alpha-bungarotoxin on seizure threshold, partially opposed the effects of gallamine and d-tubocurarine, and had no effect on the ability of apamin to reduce the seizure threshold current. Thus, both the apamin-sensitive potassium channel and a variety of distinct cholinergic mechanisms contribute in vivo to seizure genesis within the inferior collicular cortex, but not through the same mechanisms.
McCown
T J
TJ
Brain and Development Research Center, University of North Carolina, Chapel Hill 27599-7250.
Breese
G R
GR
D000818:Animals; D001030:Apamin / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004558:Electric Stimulation; D007245:Inferior Colliculi / Q000503:physiopathology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008845:Microinjections; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000503:physiopathology*; D013779:Tetrodotoxin / Q000494:pharmacology
D007457:Iodine Radioisotopes; D010276:Parasympatholytics; D011978:Receptors, Nicotinic; D001030:Apamin; D013779:Tetrodotoxin