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On the oscillatory decay of the myotonic action of 9 anthroic acid. Influence of cholinesterase inhibition

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Author: Velsen, F.L. van · Nickolson, V.J.
Type:article
Date:1977
Institution: Medisch Biologisch Laboratorium TNO Medisch Fysisch Instituut TNO
Source:European Journal of Pharmacology, 3, 42, 207-216
Identifier: 228259
Keywords: Biology · 9 Anthroic acid · Acetylcholinesterase · Adenosine triphosphatase (potassium sodium) · Cholinesterase inhibitor · Curare · Ouabain · Soman · In vitro study · Muscle contraction · Myotonia · Rat · Theoretical study · Animal · Anthracenes · Calcium · Carboxylic Acids · Chlorides · Cholinesterase Inhibitors · Diaphragm · Drug Interactions · Electric Stimulation · In Vitro · Magnesium · Male · Motor Endplate · Muscle Contraction · Neuromuscular Junction · Ouabain · Potassium · Rats · Sodium · Soman

Abstract

The effects of the myotonic agent, 9-anthroic acid (ANCA), and the acetylcholinesterase (AChE) inhibitor, soman, on the isolated phrenic nerve-diaphragm preparation of the rat were studied. ANCA induced after-contractions which followed the twitches evoked by either direct or indirect stimulation. In the intermittently stimulated muscle the height of the after-contractions decreased rather rapidly and in an oscillatory fashion. The maximum height of each after-contraction was attained after the twitch had reached its peak. AChE inhibition changed the shape of these after-contractions in the indirectly, but not in the directly stimulated diaphragm. After AChE inhibition, the after-contractions decreased more slowly and in a non-oscillatory manner. Similar phenomena were observed in vivo in the gastrocnemius-soleus muscles. The effects of ANCA in the AChE-inhibited and in the non-inhibited diaphragm could be mimicked by incubation in low chloride media. Addition of ouabain to the non-inhibited diaphragm treated with ANCA, caused an immediate and striking enhancement followed by a rapid loss of the after-contractions, whereas the twitches remained fairly constant. In the AChE-inhibited diaphragm treated with ANCA, ouabain caused no increase but only a rapid and complete decay of the after-contractions with a decrease of the twitches. It is suggested that after inhibition of the AChE in the ANCA-treated muscle fibre, the site of initiation of the repetitive action potentials which cause the after-contractions shifts from the transverse tubular system to the motor end-plate. Moreover, it is suggested that the sodium pump is involved in the gradual decay of the myotonic action of ANCA. Chemicals/CAS: 9 anthroic acid, 723-62-6; acetylcholinesterase, 9000-81-1; curare, 8063-06-7; ouabain, 11018-89-6, 630-60-4; soman, 96-64-0; Anthracenes; Calcium, 7440-70-2; Carboxylic Acids; Chlorides; Cholinesterase Inhibitors; Magnesium, 7439-95-4; Ouabain, 630-60-4; Potassium, 7440-09-7; Sodium, 7440-23-5; Soman, 96-64-0