Ionic interactions in acetylcholine contraction of the denervated rat diaphragm

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Abstract
1 The nature of the drug-receptor interaction in the acetylcholine-induced contraction of the denervated rat diaphragm was studied both by altering the external ionic environment and by determining its drug sensitivity. 2 The response to acetylcholine was insensitive to tetrodotoxin or saxitoxin, but was abolished by procaine. 3 It was unaffected by levels of MnCl2 sufficient to block the response of the innervated diaphragm to electrical stimulation, although higher levels reduced the response. The effect of Mn++ on the innervated diaphragm was overcome by raising the external Ca++ level; this was ineffective in the denervated preparation. 4 In spite of its insensitivity to tetrodotoxin the acetylcholine contraction was reduced and prolonged by low external Na+ levels. This prolongation was not found when Li+ substituted for Na+. 5 Increasing the external level of Ca++ or Mg++ 3 to 5-fold reduced the acetylcholine contraction; high Ca++ also prolonged it. Reduction in the divalent cation level was without effect. 6 Procaine inhibition of the acetylcholine response was largely competitive, as was inhibition due to (+)-tubocurarine. This was shown by probit analysis and the dose-ratio test. 7 Thiocyanate (12 mm) augmented and prolonged the contraction; this action was modified by altering the Ca++ or Mg++ level of the solution. 8 The acetylcholine receptor resembles that of the innervated postsynaptic membrane.