The influence of pH on the effects of organic anions in frog skeletal muscle

1977 ◽  
Vol 55 (5) ◽  
pp. 1122-1134 ◽  
Author(s):  
J. G. Foulks ◽  
Florence A. Perry ◽  
P. Tsang
Keyword(s):  
Skeletal Muscle ◽  
Divalent Cations ◽  
Organic Anions ◽  
Frog Skeletal Muscle ◽  
Depressant Effect ◽  
Contractile Responses ◽  
Neutral Ph ◽  
Acid Ph ◽  
Depressant Action ◽  
Carboxylate Anions

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.

Some effects of organic anions on excitability and excitation–contraction coupling in frog skeletal muscle

1977 ◽  
Vol 55 (3) ◽  
pp. 700-708 ◽  
Author(s):  
J. G. Foulks ◽  
Florence A. Perry
Keyword(s):  
Skeletal Muscle ◽  
Divalent Cations ◽  
Membrane Surface ◽  
Organic Anions ◽  
Polar Group ◽  
Frog Skeletal Muscle ◽  
Excitation Contraction Coupling ◽  
Partial Restoration ◽  
Contraction Coupling ◽  
Contractile Performance

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.

Increased sensitivity of frog skeletal muscle to procaine in the presence of organic anions

1978 ◽  
Vol 56 (5) ◽  
pp. 739-746 ◽  
Author(s):  
J. G. Foulks ◽  
F. A. Perry
Keyword(s):  
Action Potentials ◽  
Time Course ◽  
Organic Anion ◽  
Organic Anions ◽  
Depressant Effect ◽  
Alkyl Sulfonates ◽  
Carboxylate Anions ◽  
Increased Sensitivity ◽  
Local Anaesthetic Action ◽  
Anaesthetic Action

In solutions containing an organic anion in place of chloride, frog toe muscles displayed increased sensitivity to the local anaesthetic action of procaine. Twitch inhibition by procaine in all media was accompanied by suppression of action potentials without change in membrane resting potentials. The twitch depressant effect of procaine was greater in solutions with carboxylate anions than with alkyl sulfonates. The intensity and the rapidity of onset of the effects of organic anions was related to the size of their hydrophobic component.Procaine accentuated acetate-induced reductions in the [K]0 required to produce K contractures and in the time course of submaximum K contractures. These effects were not shared by benzocaine. They were antagonized by increased [Ca]0.The results indicate that separate agents can exert mutually enhancing actions from opposite surfaces of the sarcolemma to facilitate the inactivation of depolarization-induced excitation–contraction coupling as well as that of the potential-dependent sodium channel.

The influence of D2O, perchlorate, and variation in temperature on the potential-dependent contractile function of frog skeletal muscle

1985 ◽  
Vol 63 (6) ◽  
pp. 693-703
Author(s):  
James G. Foulks ◽  
Lillian Morishita
Keyword(s):  
Skeletal Muscle ◽  
Contractile Function ◽  
Divalent Cations ◽  
Conformational Transitions ◽  
The Other ◽  
Frog Skeletal Muscle ◽  
Solvent Structure ◽  
Opposing Effects ◽  
Kinetics Of ◽  
Reduced Temperature

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.

Enhancement (by ATP, insulin, and lack of divalent cations) of ouabain inhibition of cation transport and ouabain binding in frog skeletal muscle; effect of insulin and ouabain on sarcolemmal (Na + K)MgATPase

1977 ◽  
Vol 55 (1) ◽  
pp. 21-33 ◽  
Author(s):  
J. F. Manery ◽  
E. E. Dryden ◽  
J. S. Still ◽  
G. Madapallimattam
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Space ◽  
Divalent Cations ◽  
Membrane Surface ◽  
Cation Transport ◽  
Frog Skeletal Muscle ◽  
Ouabain Binding ◽  
Maximum Inhibition ◽  
Ouabain Inhibition ◽  
External K

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.

Restoration of the Ability of Frog Skeletal Muscle to Develop Potassium Contractures in Calcium-Deficient Media

1973 ◽  
Vol 51 (5) ◽  
pp. 335-343 ◽  
Author(s):  
J. G. Foulks ◽  
J. A. D. Miller ◽  
Florence A. Perry
Keyword(s):  
Skeletal Muscle ◽  
Contractile Function ◽  
Divalent Cations ◽  
Frog Skeletal Muscle ◽  
Free Media ◽  
Dependent Processes

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.

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
Keyword(s):  
Skeletal Muscle ◽  
Hydrophobic Interactions ◽  
Contractile Function ◽  
Divalent Cations ◽  
Frog Skeletal Muscle ◽  
Twitch Potentiation ◽  
Low Concentrations ◽  
Small N ◽  
Potential Threshold ◽  
Caffeine Contractures

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.

scholarly journals Mechanical Threshold As a Factor in Excitation-Contraction Coupling

1969 ◽  
Vol 54 (3) ◽  
pp. 352-368 ◽  
Author(s):  
Stuart R. Taylor ◽  
Hanna Preiser ◽  
Alexander Sandow
Keyword(s):  
Skeletal Muscle ◽  
Electromechanical Coupling ◽  
Divalent Cations ◽  
Direct Action ◽  
Type A ◽  
Frog Skeletal Muscle ◽  
Tension Development ◽  
Contraction Coupling ◽  
Mechanical Threshold ◽  
Coupling Processes

I-, CH3SO4-, and ClO4-, like other previously studied type A twitch potentiators (Br-, NO3-, SCN-, and caffeine), lower the mechanical threshold in K depolarization contractures of frog skeletal muscle. In potentiated twitches, I-, Br-, CH3SO4-, ClO4, and SCN, as already reported for NO3- and caffeine, slightly shorten the latent period (L) and considerably increase the rate of tension development (dP/dt) during the first few milliseconds of the contraction period. Divalent cations (8 mM Ca2+, 0.5–1.0 mM Zn2+ and Cd2+) raise the mechanical threshold of contractures, and correspondingly affect the twitch by depressing the tension output, increasing L, and decreasing the early dP/dt, thus acting oppositely to the type A potentiators. These various results form a broad, consistent pattern indicating that electromechanical coupling in the twitch is conditioned by a mechanical threshold as it is in the contracture, and suggesting that the lower the threshold, in reference to the raised threshold under the action of the divalent cations, the more effective is a given action potential in activating the twitch as regards especially both its early rate and peak magnitude of tension development. The results suggest that the direct action by which the various agents affect the level of the mechanical threshold involves effects on E-C coupling processes of the T tubular and/or the sarcoplasmic reticulum which control the release of Ca for activating contraction.

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