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Abstract

gamma-Aminobutyric acid type A receptor antagonists picrotoxin and bicuculline alter acetylcholine channel kinetics in cultured embryonic rat skeletal muscle.

Q Y Liu, V Dunlap and J L Barker
Molecular Pharmacology December 1994, 46 (6) 1197-1203;
Q Y Liu
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V Dunlap
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J L Barker
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Abstract

The effects of the classical gamma-aminobutyric acid type A receptor antagonists picrotoxin and bicuculline on nicotinic acetylcholine receptors in cultured embryonic rat skeletal muscle were examined with whole-cell and cell-attached single-channel recording methods. Up to 600 microM picrotoxin had little or no effect on the amplitude of the whole-cell current, whereas bicuculline dose-dependently blocked it, with an IC50 value of 101.2 +/- 8.9 microM. Bicuculline reduced the maximum inducible acetylcholine current without changing the Kd value, suggesting that bicuculline uncompetitively blocked the binding of acetylcholine to its receptor. The elementary nicotinic acetylcholine receptor currents recorded in the cell-attached single-channel recording configuration exhibited properties typical of those recorded in embryonic muscle (approximately 36 pS and approximately 6 msec). Picrotoxin dramatically transformed individual channel openings into briefly interrupted bursts, so that the number of openings increased while the mean open time markedly decreased. Bicuculline decreased mean open time to a lesser but statistically significant degree. The dominant component of the closed time histogram in control recordings occurred at 17 msec, whereas that recorded with picrotoxin occurred at 0.5 msec. Bicuculline prolonged the closed time, with a dominant closed time component at 52 msec. Elementary conductance was not altered by either agent. In conclusion, we found that the gamma-aminobutyric acid type A channel antagonists picrotoxin and bicuculline were also blockers of embryonic nicotinic acetylcholine receptor channels in cultured rat muscle.

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Molecular Pharmacology
Vol. 46, Issue 6
1 Dec 1994
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Abstract

gamma-Aminobutyric acid type A receptor antagonists picrotoxin and bicuculline alter acetylcholine channel kinetics in cultured embryonic rat skeletal muscle.

Q Y Liu, V Dunlap and J L Barker
Molecular Pharmacology December 1, 1994, 46 (6) 1197-1203;

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Abstract

gamma-Aminobutyric acid type A receptor antagonists picrotoxin and bicuculline alter acetylcholine channel kinetics in cultured embryonic rat skeletal muscle.

Q Y Liu, V Dunlap and J L Barker
Molecular Pharmacology December 1, 1994, 46 (6) 1197-1203;
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