Ionic Influences on Succinylcholine Blockade of the Mammalian Neuromuscular Junction

Self Cite

A ustralia 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 deternining 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 MnCl. 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+4 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 inhilbition 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.

Section: Methodsmentioning

confidence: 93%

“…The standard nutrient solution used has been described elsewhere (Freeman, 1968). Na+-free solutions were buffered with tris(hydroxymethyl)aminomethane hydrochloride (Tris).…”

Section: Methodsmentioning

confidence: 99%

Ionic interactions in acetylcholine contraction of the denervated rat diaphragm

Freeman¹,

Turner²

1969

Self Cite

“…This loss of distinguishing characteristics is probably related to the changes in ion permeability which occur in isolated tissues (Creese & Northover, 1961;Krnjevic & Miledi, 1958), and also to the way in which the drug reaches the receptor sites (Gibberd, 1966). The most obvious characteristic common to all isolated nerve-muscle preparations is the biphasic response of the muscle to the continuing presence of the blocking agent (Jenden, Kamijo & Taylor, 1954;Jenden, 1955;Sabawala & Dillon, 1959;Maclagan, 1962;Taylor, 1962;Whittaker, 1962a, Freeman, 1968a. This response in particular has led to many of the current theories of the mechanism of depolarizing blockade in isolated nerve-muscle preparations.…”

Section: Discussionmentioning

confidence: 99%

The effect of some foreign anions on suxamethonium blockade of the isolated rat diaphragm preparation

Harris

Leach

1970

Summary1. The pharmacology of suxamethonium blockade of the rat phrenic nervediaphragm preparation has been studied in the presence of some foreign anions. 2. Blockade proceeded in two distinct phases in both normal and modified Krebs solution.3. In normal Krebs solution the characteristics bore no close resemblance to either depolarizing or competitive type blockade. 4. In the presence of foreign anions the characteristics of the blockade more closely resembled those of depolarization. 5. There was an increase in the sensitivity of the motor end-plate region of the muscle to the depolarizing action of acetylcholine, carbachol and suxamethonium in the presence of the anions. 6. Although the anions enhanced the depolarizing activity of suxamethonium, the blocking potency of the drug was unaltered. 7. It is suggested that end-plate depolarization plays little part in suxamethonium blockade of the isolated rat diaphragm and that desensitization is the primary cause of the blockade.

“…This development of tolerance is in contrast to the findings of Hansson (1958), who did not observe tachyphylaxis to suxamethonium in horses under pentobarlbitone anaesthesia, and to the findings of Thesleff (1952) and Conway (1961) in the cat. Tachyphylaxis to the neuromuscular blocking and cardiovascular effects of suxamethonium has been recorded, however, iby other workers in isolated muscle preparations (Freeman, 1967), and in the intact dog (Stevenson, 1960a), cat (Adams & Hall, 1962), and man (Graf et al, 1963).…”

Section: Discussionmentioning

confidence: 99%

The influence of suxamethonium on cardiovascular and respiratory function in the anaesthetized horse

Lees

Tavernor

1969

1. In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short-lived period of hypoventilation, which was associated with increases in arterial blood Pco, levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and Po, values. 2. The respiratory depressant action of suxamethonium chloride 02 mg/kg was accomipanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater changes in cardiovascular and respiratory function. These effects were not accompanied by cardiac arrhythmias, with the exception of one animal, in which an unusually prolonged period of apnoea occurred. 3. The cardiovascular effects of suxamethonium during halothane anaesthesia were diminished but not abolished when the respiratory depressant action of suxamethonium was prevented by applying positive pressure ventilation. 4. The cardiovascular effects of suxamethonium in horses anaesthetized with halothane were partially antagonized by propranolol and completely antagonized by hexamethonium. It is suggested that the cardiovascular effects of suxamethonium are mediated by two distinct mechanisms: reflexly mediated increases in heart rate and sympathetic vasoconstrictor tone due to the respiratory depression, and a direct stimulant action of suxamethonium on peripheral. autonomic ganglia. 5. Much less pronounced changes in cardiovascular function, but not in respiratory function, were recorded when suxamethonium was administered to horses anaesthetized with ether. 6. A slight degree of tachyphylaxis to the cardiovascular and respiratory effects of suxamethonium was recorded in horses anaesthetized with halothane. 7. Some atypical effects of suxamethonium on respiration are described.The reported side effects of suxamethonium in laboratory animals include tachycardia, bradycardia and changes, usually of a pressor nature, in mean arterial blood pressure. In addition, cardiac arrhythmias have also been recorded following the administration of suxamethonium to monkeys, cats, dogs and rabbits