Calcium-dependent actions of the convulsant barbiturate, CHEB, on transmitter release at the rat neuromuscular junction.
1. The effect of convulsant barbiturates on spontaneous and evoked acetylcholine release was studied at the rat neuromuscular junction in vitro. 2. The convulsant barbiturates (+)-5-(1,3-dimethylbutyl)-5-ethyl barbituric acid [(+)-DMBB], 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB), 5-ethyl-5-(3-methylbut-2'-enyl) barbituric acid (3M2B) and 5-ethyl-5-(1,3-dimethylbut-1'-enyl) barbituric acid (1,3M1B) all produced a concentration-dependent increase in miniature end-plate potential (MEPP) frequency. 3. With CHEB (100 microM) this increase in MEPP frequency was found to be dependent on the [Ca2+]o. CHEB in 0.5 mM [Ca2+]o did not alter MEPP amplitude, but in 1.3 and 2.5 mM [Ca2+]o CHEB significantly reduced the amplitude. 4. At a [Ca2+]o of 0.5 mM, CHEB produced an increase in both EPP amplitude and quantal content, while at 1.3 mM [Ca2+]o CHEB did not alter EPP amplitude or quantal content. 5. The plot of log quantal content vs log [Ca2+]o showed a parallel shift to the left in the presence of 100 microM CHEB. This change occurred without any alteration in the maximum quantal content. This suggests that the enhancement of transmitter release may be mediated by an effect on calcium fluxes in the pre-junctional nerve terminal.
Nicholson
G M
GM
Department of Pharmacology, University of Sydney, N.S.W., Australia.
Spence
I
I
Johnston
G A
GA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001463:Barbiturates / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001463:Barbiturates; D003292:Convulsants; D018377:Neurotransmitter Agents; C024321:5-(2-cyclohexylidene-ethyl)-5-ethylbarbiturate; D000109:Acetylcholine; D002118:Calcium