A comparison of the effects of cationic, anionic, and neutral amphipathic agents on the contractile behaviour of frog skeletal muscle. I. Twitches and potential threshold for contraction

1984 ◽  
Vol 62 (12) ◽  
pp. 1348-1355
Author(s):  
James G. Foulks ◽  
Lillian Morishita

Cationic, anionic, and neutral amphipathic agents displayed striking differences as well as similarities in their effects on the contractile function of frog skeletal muscle. Slowed repolarization during the action potential appeared to account for twitch potentiation by low concentrations of alkyl trimethylammonium and by small n-alkanols (propanol, butanol). Small n-alkanols also caused a decrease in the potential threshold for K contractures and slower relaxation of submaximum K contractures as well as enhancement of chloride withdrawal and caffeine contractures, but these effects were not observed with larger alkanols. For the ionic amphipathic agents, the direction of the changes in the relation between K0 and K-contracture tension could be accounted for on the basis of the expected changes in surface charge, but the effects of these two types of agents on the rate of relaxation of submaximum K contractures were disproportionate and with the cationic series were opposite in direction to those produced by inorganic divalent cations. The reductions in the amplitude of chloride-withdrawal contractures by cationic as well as anionic amphipaths indicated that both types of agents can impair excitation–contraction coupling. Similar depressant effects on caffeine contractures demonstrate that these responses also can be influenced by events restricted to the external lamina of the sarcolemma. It is concluded that opposite effects can be produced by similar perturbations in different regions of the sarcolemma and that electrostatic as well as hydrophobic interactions can make an important contribution to the effects of amphipathic agents on twitches and contractures in skeletal muscle.

1985 ◽  
Vol 63 (6) ◽  
pp. 693-703
Author(s):  
James G. Foulks ◽  
Lillian Morishita

D2O and perchlorate manifest opposing effects on the contractile function of skeletal muscle (amplitude of twitches and maximum K contractures, potential dependence of contraction activation and inactivation), and when combined the influence of one may effectively antagonize that of the other. The ratio of perchlorate concentrations required to produce effects of equal intensity (e.g., twitch enhancement and restoration of maximum K contractures in media lacking divalent cations or containing a depressant concentration of a cationic amphipath) in H2O and D2O solutions was generally rather constant. These findings are compatible with the view that both agents can influence contractile function by virtue of their effects on solvent structure. In the absence of divalent cations, the effects of reduced temperature resemble those of D2O whereas the effects of increased temperature resemble those of the chaotropic anion. However, in other media, variation in temperature was found to result in additional nonsolvent effects so that low temperature could oppose rather than enhance the effects of D2O. These observations are discussed in terms of a model which postulates a role for solvent influences on the kinetics of two separate potential-dependent conformational transitions of membrane proteins which mediate the activation and inactivation of contraction in skeletal muscle.


1973 ◽  
Vol 51 (5) ◽  
pp. 335-343 ◽  
Author(s):  
J. G. Foulks ◽  
J. A. D. Miller ◽  
Florence A. Perry

A number of agents were tested for their ability to restore potassium (K) contractures in calcium-free media. Effective agents included caffeine, chloroform, more polar permeant anions (e.g. nitrate and perchlorate) in place of external chloride, as well as divalent cations, e.g. Mg2+. The presence of sufficient EGTA to preclude significant increases in [Ca]0 did not affect the extent of K contracture restoration produced by these agents. The loss of K contracture capacity in calcium-free media, and its restoration by effective agents, appear to be related to the disproportionate effect of these procedures on the relation between log [K]0 and the potential-dependent processes which regulate contractile function.


1984 ◽  
Vol 62 (12) ◽  
pp. 1356-1364
Author(s):  
James G. Foulks ◽  
Lillian Morishita

Sufficiently high concentrations of cationic (n-alkyl trimethylammonium) or neutral (n-alkanols) amphipathic agents reduced the amplitude of maximum K contractures of frog toe muscles, an effect which was antagonized by reduced temperature, by the presence of perchlorate anions, or (to a lesser extent) by an increased concentration of divalent cations. Enhancement of the similar effect of tetracaine was prominent only with alkyl trimethylammonium compounds. Enhancement of the depressant effect of acidity (pH 5.0) was observed with octyl trimethylammonium and octanol but not with octanesulfonate or butanol. Partial restoration of potassium contractures in media lacking divalent cations was produced by octane- or nonane-sulfonate and by propanol but not by octyl trimethylammonium or octanol. The alkyl sulfonates differed from the other agents studied in producing tonic contractures at concentration which did not reduce maximum K-contracture tension. The alkyl sulfonates also differed from other amphipaths of similar size in their ability to elicit small repolarization-induced contractures in the absence of perchlorate, although this property also was shared by small alkanols. Sufficient concentrations of all amphipaths reduced the amplitude of repolarization-induced contractures in the presence of perchlorate. The intensity of the effects of these agents on contractile function usually was proportional to the size of their apolar group, and with ionic apmphipaths such effects were apparent only with compounds having hydrocarbon chains containing eight or more carbon atoms. These experiments indicate that hydrophobic interactions in the external lamina of the sarcolemma can influence the potential-dependent control of contractile function in skeletal muscle, presumably by effects on the conformational transitions of integral membrane proteins. The similarity between many of the effects of alkyl sulfonate and small n-alkanols as well as those of small concentrations of perchlorate suggest that chaotropic actions can contribute to these effects. The difference between the effects of anionic and cationic agents, as well as between the effects of n-alkanols of different size may be attributable to the different intensity of similar effects at different membrane sites.


1974 ◽  
Vol 52 (6) ◽  
pp. 1126-1135 ◽  
Author(s):  
D. J. Parry ◽  
A. Kover ◽  
G. B. Frank

Exposure of frog toe muscles to 1 mM La3+ results in a decrease in amplitude and rate of tension development of potassium contractures and twitches. At this concentration La3+ also inhibits the uptake of calcium, both in the resting condition and during stimulation. Caffeine contractures are unaffected even after a 5-min pre-exposure to La3+. The depolarization induced by various concentrations of K+ is reduced by about 10 mV as is the amplitude of the action potential. The rate of rise of the action potential is reduced by about 40% after 1 min in La3+ Ringer. Neither the decreased amplitude nor the reduced rate of depolarization is considered to be sufficient to explain the inhibition of tension development. It is suggested that La3+ partially uncouples excitation from contraction by preventing the release of a trigger-Ca2+ fraction from some site on the muscle membrane. This fraction normally plays a role in excitation–contraction coupling, although some tension may still be developed in the absence of a trigger-Ca2+ influx.


1977 ◽  
Vol 55 (5) ◽  
pp. 1122-1134 ◽  
Author(s):  
J. G. Foulks ◽  
Florence A. Perry ◽  
P. Tsang

The depressant effect of acidity on twitches and K contractures in frog skeletal muscle was greatly accentuated in the presence of organic anions, particularly anions such as butyrate, which also reduced these responses at neutral pH. Conversely, alkaline pH antagonized the depression of contractile responses by butyrate. Most of the effects of acid pH were rapid in onset and were accomplished without any change in membrane resting or action potentials, although depolarization developed in the presence of carboxylate anions when pH was reduced below 6.0. Simultaneous variation in pH and butyrate concentration showed that the undissociated acid exerted a prominent depressant effect only when its concentration reached 1–10 mM, and that the marked depressant action of butyrate at neutral pH was produced primarily by the dissociated anion. Similar experiments showed that the dissociated anion also was largely responsible for the enhanced depolarizing effect of acidity in media containing carboxylates. Acid-induced depolarization was not facilitated in media containing methane sulfonate, but in spite of its low pKa, this anion also increased the sensitivity of contractile responses to the depressant effects of acidity. Hence, the accentuation of the effects of organic anions by acid pH must be exerted on the sequence of membrane events which link excitation and contraction. The effect of acidity was greater when longer apolar hydrocarbon chains were attached to the anionic group for both the carboxylate and the sulfonate series of ions. These depressant effects may be produced by interference with the membrane-stabilizing actions of divalent cations, and may involve increased membrane fluidity.


1978 ◽  
Vol 56 (3) ◽  
pp. 501-508 ◽  
Author(s):  
G. B. Frank ◽  
J. Marwaha

Extracellular and intracellular microelcctrode studies were conducted to test the actions and interactions of opiate agonists, antagonists, and procaine on action potentials in frog sartorius muscles. Extracellular studies showed that morphine, methadone, propoxyphene, and procaine all depressed action potential production. Low concentrations of naloxone or naltrexone antagonized the excitability depression produced by the three opiate agonists but not the depression produced by procaine. Intracellular studies revealed that certain concentrations of the opiate agonists produced a biphasic decline in the stimulus-induced increase in sodium conductance (gNa). Naloxone or naltrexone antagonized only the second phase of this decline. These results show that part of the excitability depression produced by opiate agonists is due to an action on opiate drug receptors.


1988 ◽  
Vol 92 (5) ◽  
pp. 601-612 ◽  
Author(s):  
L Csernoch ◽  
C L Huang ◽  
G Szucs ◽  
L Kovacs

The effects of tetracaine on charge movements and on antipyrylazo III signals monitoring intracellular delta [Ca2+] were compared in cut frog semitendinosus muscle fibers in a single vaseline gap-voltage clamp. Low tetracaine concentrations (25-40 microM) markedly reduced delta [Ca2+] signals and shifted the rheobase. However, they neither influenced charge movement nor that peak delta [Ca2+] value associated with the contractile threshold. Higher tetracaine concentrations (100-200 microM) partly inhibited charge movements in cut fibers. They separated a steeply voltage-sensitive charge, some of whose features resembled 'q gamma' reported in intact fibers, and whose movement preceded delta [Ca2+] signals at threshold. These findings: (a) directly confirm an earlier suggestion that tetracaine acts on steps in excitation-contraction coupling rather than myofilament activation; (b) show that tetracaine at low concentrations can directly interfere with sarcoplasmic reticular calcium release without modifying charge movement; (c) show that the tetracaine-sensitive charge, first found in intact fibers, also exists in cut fibers; and (d) make it unlikely that tetracaine-sensitive charge transfer is a consequence of Ca2+ release as suggested on earlier occasions.


1977 ◽  
Vol 55 (1) ◽  
pp. 21-33 ◽  
Author(s):  
J. F. Manery ◽  
E. E. Dryden ◽  
J. S. Still ◽  
G. Madapallimattam

Using small, intact frog muscles, the basic properties of Na+ and K+ transport were shown to resemble those of the (Na+ + K+) Mg2+ATPase (EC 3.6.1.3) isolated from skeletal muscle, (a) External K+ is essential for Na+ exit and K+ entry after the muscles are Na+-loaded and K+-depleted; (b) the ouabain concentration causing maximum inhibition of recovery is the same for transport as for the inhibition of the isolated enzyme. Ouabain causes a decrease in the sorbitol space and causes muscle fibre swelling. Absence of Ca2+ and Mg2+ inhibits recovery of normal Na+ and K+ concentrations and increases the sorbitol space. Insulin stimulates K+ uptake and Na+ loss in intact muscles but has no effect on the isolated sarcolemmal (Na+ + K+) Mg2+ATPase. Absence of divalent cations, addition of external ATP and of insulin enhance the ouabain inhibition of recovery.Bound ouabain was measured using [3H]ouabain and [14C]sorbitol (to measure the extracellular space). The process of binding was slowly reversible and was saturable within a range of ouabain concentrations from 1.48 × 10−7 to 5.96 × 10−7 M. From the nonexchangeable ouabain bound, the density of glycoside receptors was estimated to be 650 molecules per square micrometre of membrane surface. The absence of divalent cations, addition of external ATP and of insulin significantly enhanced the amount of ouabain bound. Substitution of Na+ and K+ by choline greatly reduced the bound ouabain.


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