The effects of acute and chronic botulinum toxin treatment on receptor number, receptor distribution and tissue sensitivity in rat diaphragm

Abstract

Tritiated alpha-bungarotoxin was used to determine the number and distribution of acetylcholine receptors in innervated, denervated and botulinum toxin-treated muscles. Innervated hemidiaphragms bound approximately 2.3 x 10(11) molecules of alpha-bungarotoxin; binding sites were restricted to the end-plate region. Neither acute denervation nor acute poisoning with botulinum toxin altered the number or distribution of alpha-bungarotoxin binding sites. In chronically denervated hemidiaphragms, there was an increase in alpha-bungarotoxin binding sites (maximum about 5.7 x 10(12); these sites were distributed across the muscle surface. In chronically poisoned hemidiaphragms, there was also an increase in the number (maximum about 4.7 x 10(12)) and distribution of binding sites. Chronic denervation and chronic botulinum toxin treatment both produced supersensitivity to acetylcholine. At maximal sensitivity, the respective ED50 values were: denervated muscle, 1.1 x 10(-6) M; botulinum toxin-treated muscle, 5.0 x 10(-6) M. The combination of denervation plus botulinum toxin treatment did not have additive or synergistic effects on alpha-bungarotoxin binding (4.9 x 10(12) molecules/hemidiaphragm) or on tissue sensitivity to acetylcholine (ED50 = 2.1 x 10(-6) M). It is concluded that denervation and botulinum toxin have rather similar effects on the number and distribution of acetylcholine receptors in rat hemidiaphragm.