A comparison of the local anaesthetic effects of cationic, anionic, and neutral amphipathic agents in frog skeletal muscle

1984 ◽  
Vol 62 (4) ◽  
pp. 345-349
Author(s):  
James G. Foulks ◽  
Lillian Morishita

Impermeant alkyl amphipathic agents reduced the excitability of frog twitch muscle fibers, indicating that local anaesthesia can be produced by perturbations within the external lamina of the sarcolemma. Cationic (n-alkyl trimethylammonium) and anionic (n-alkyl sulfonate) as well as permeant neutral (n-alkanol) agents have been compared with regard to their local anaesthetic potency. Small impermeant agents (fewer than six carbon atoms) alone were ineffective. Within each series the concentration required to reduce excitability was proportional to the length (hydrophobicity) of the hydrocarbon chain attached to the polar group. However, corresponding members of these three series of compounds differed considerably in their local anaesthetic potency. Hence, charged groups as well as apolar moieties can influence local anaesthetic efficacy. The supra-additive character of the local anaesthesia produced by combining impermeant alkyl anions and cations indicates that these two types of amphipaths may produce their similar effects by perturbations at different membrane sites.

1977 ◽  
Vol 55 (3) ◽  
pp. 700-708 ◽  
Author(s):  
J. G. Foulks ◽  
Florence A. Perry

When substituted for external chloride, organic anions differed markedly from one another in the extent to which they produced hyperexcitability and in the direction and intensity of their effects on twitch tension in frog skeletal muscle. All of the anions studied reduced the threshold [K]0 for K contractures and most enhanced twitch tension. Among carboxylate anions, increasing the size of the attached apolar hydrocarbon chain led to decreased hyperexcitability and to reduction in the amplitude of twitches and maximum K-contractures, butyrate being the most effective depressant of these responses. Sulfonate anions produced much less conspicuous changes in contractile performance. With γ-hydroxybutyrate, the introduction of a polar group on the hydrocarbon terminus resulted in twitch enhancement and partial restoration of maximum K-contracture tension. The depressant effect of butyrate on K contractures was partially overcome by a fivefold increase in the external concentration of calcium but twitches were unaffected. Perchlorate (12 mM) effectively antagonized the depressant actions of butyrate on twitches as well as K contractures. Most of the effects of these anions were prompt in onset. Impairment of contractile performance by butyrate was not accompanied by appreciable changes in membrane resting or action potentials or in the relation between [K]0 and membrane potential, and took place in spite of reduction in K-contracture threshold. Such effects must result from alteration in excitation–contraction coupling, possibly by interference with the binding of divalent cations to the membrane surface.


1984 ◽  
Vol 106 (3) ◽  
pp. 336-337 ◽  
Author(s):  
Bengt Hallengren ◽  
Arne Melander ◽  
Stephen Thesleff

Abstract. Propylthiouracil (PTU) and propranolol can suppress, while methimazole (MMI) can enhance, mitogenie activation of lymphocytes. The present study investigated whether this effect of PTU, as has been shown for propranolol, relates to local anaesthetic activity. MMI (1 mm) but not PTU (1 mm) reduced the action potential in rat skeletal muscle. Thus, PTU seems to lack local anaesthetic activity. Moreover, the recorded local anaesthetic capacity of MMI hardly explains the stimulatory influence of MMI on lymphocyte activation. Apparently, the interference of MMI and PTU with lymphocyte activation seems to be due to another mechanism than local anaesthetic activity.


Author(s):  
Joachim R. Sommer ◽  
Nancy R. Wallace

After Howell (1) had shown that ruthenium red treatment of fixed frog skeletal muscle caused collapse of the intermediate cisternae of the sarcoplasmic reticulum (SR), forming a pentalaminate structure by obi iterating the SR lumen, we demonstrated that the phenomenon involves the entire SR including the nuclear envelope and that it also occurs after treatment with other cations, including calcium (2,3,4).From these observations we have formulated a hypothesis which states that intracellular calcium taken up by the SR at the end of contraction causes the M rete to collapse at a certain threshold concentration as the first step in a subsequent centrifugal zippering of the free SR toward the junctional SR (JSR). This would cause a) bulk transport of SR contents, such as calcium and granular material (4) into the JSR and, b) electrical isolation of the free SR from the JSR.


Author(s):  
A. V. Somlyo ◽  
H. Shuman ◽  
A. P. Somlyo

Electron probe analysis of frozen dried cryosections of frog skeletal muscle, rabbit vascular smooth muscle and of isolated, hyperpermeab1 e rabbit cardiac myocytes has been used to determine the composition of the cytoplasm and organelles in the resting state as well as during contraction. The concentration of elements within the organelles reflects the permeabilities of the organelle membranes to the cytoplasmic ions as well as binding sites. The measurements of [Ca] in the sarcoplasmic reticulum (SR) and mitochondria at rest and during contraction, have direct bearing on their role as release and/or storage sites for Ca in situ.


1990 ◽  
Vol 21 (6) ◽  
pp. 863-868 ◽  
Author(s):  
Péter P. Nánási ◽  
Tamás Kiss ◽  
Miklós Dankó ◽  
David A. Lathrop

1961 ◽  
Vol 44 (6) ◽  
pp. 1159-1164 ◽  
Author(s):  
Eugene M. Renkin

Using choline-methyl-C14 as a tracer, it has been shown that choline+ penetrates into the cells of resting frog skeletal muscle at a rate similar to that of Na+, and that it escapes from these cells much more slowly than does Na+. Some implications of these findings are discussed.


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