BAY K 8644 and nifedipine alter halothane but not caffeine contractures of malignant hyperthermic muscle fibers

1991 ◽  
Vol 261 (4) ◽  
pp. R782-R786
Author(s):  
J. H. Williams ◽  
M. Holland ◽  
J. C. Lee ◽  
C. W. Ward ◽  
C. J. McGrath
Keyword(s):  
Skeletal Muscle ◽  
Ethylene Glycol ◽  
Onset Time ◽  
Bay K 8644 ◽  
Fiber Bundles ◽  
Tetraacetic Acid ◽  
Mechanical Responses ◽  
Resting Tension ◽  
Malignant Hyperthermia Susceptible ◽  
Caffeine Contractures

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.

Inositol trisphosphate enhances calcium release in skinned cardiac and skeletal muscle

1986 ◽  
Vol 250 (5) ◽  
pp. C807-C811 ◽  
Author(s):  
T. M. Nosek ◽  
M. F. Williams ◽  
S. T. Zeigler ◽  
R. E. Godt
Keyword(s):  
Skeletal Muscle ◽  
Calcium Release ◽  
Inositol Trisphosphate ◽  
Calcium Sensitivity ◽  
Fiber Bundles ◽  
Tetraacetic Acid ◽  
Contractile Apparatus ◽  
Semitendinosus Muscle ◽  
Skinned Cardiac Fibers ◽  
Caffeine Contractures

Experiments from other laboratories suggest that inositol trisphosphate (InsP3) may be involved in the excitation-contraction coupling (ECC) process of cardiac and skeletal muscle. Our results support this hypothesis. Studying fiber bundles (less than 200-microns diameter) from guinea pig papillary muscles skinned with saponin and mechanically skinned single fibers from frog semitendinosus muscle, we find that calcium-induced force oscillations (observed in solutions containing low ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid and pCa 7.0) are enhanced in magnitude and frequency by InsP3 at concentrations as low as 1 microM. InsP3 at 10 microM can often induce such oscillations in mechanically skinned frog skeletal muscle. In skinned cardiac fibers, InsP3 increases the magnitude of caffeine contractures at submaximal caffeine concentrations to a greater extent than at near-maximal caffeine concentrations. InsP3 (30 microM) has no effect on either the calcium sensitivity or maximal force generated by the contractile apparatus of skinned cardiac muscle. We conclude that InsP3 has no direct effect on the contractile machinery but that it can modulate ECC by enhancing the calcium-induced release of calcium from the sarcoplasmic reticulum, possibly from the same pool and through the same mechanism as caffeine.

Two structural states of Z-bands in cardiac muscle

1989 ◽  
Vol 256 (2) ◽  
pp. H552-H559 ◽  
Author(s):  
M. A. Goldstein ◽  
L. H. Michael ◽  
J. P. Schroeter ◽  
R. L. Sass
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Skeletal Muscles ◽  
Optical Diffraction ◽  
Square Lattice ◽  
Tetraacetic Acid ◽  
Repeat Distance ◽  
Thin Filaments ◽  
Resting Tension ◽  
Rat Papillary Muscle

We have compared the form and dimensions of the Z-band lattice in rat papillary muscle fixed at rest with and without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) using electron microscopy and optical diffraction. In unstimulated muscle, the Z-band lattice form called basket weave predominated, and the Z-spacing (defined as the repeat distance of a tetragonal array of cross-cut thin filaments from the same sarcomere) was 23.93 +/- 0.37 nm. Muscles exposed to EGTA exhibited the small square-lattice form, and the Z-spacing was 20.50 +/- 0.19 nm. The Z-spacings in the two lattice forms were similar in cardiac and skeletal muscles such that the decrease in Z-spacing in the transition from basket weave to small square in this study was similar to the increase in Z-spacing previously demonstrated in skeletal muscle in the transition from small square to basket weave. The Z-lattice form and dimensions in unstimulated cardiac muscle resembled those in tetanized skeletal muscle. These findings are consistent with the higher resting tension in cardiac muscle and suggest that Ca2+ may be important for the maintenance of the expanded Z-lattice form.

Effects of BAY K 8644, nifedipine, and low Ca2+ on halothane and caffeine potentiation

1991 ◽  
Vol 71 (2) ◽  
pp. 721-726 ◽  
Author(s):  
J. H. Williams ◽  
M. Holland ◽  
J. C. Lee ◽  
C. W. Ward ◽  
K. P. Davy
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Fiber Bundles ◽  
Mammalian Skeletal Muscle ◽  
Inotropic Effects ◽  
Twitch Potentiation

The purpose of this investigation was to examine the effects of the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine on halothane- and caffeine-induced twitch potentiation of mammalian skeletal muscle. Muscle fiber bundles were taken from normal Landrace pigs and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), and low Ca2+ media administered alone and in combination with halothane (3%) or with increasing concentrations of caffeine (0.5–8.0 mM). Both BAY K 8644 and halothane potentiated twitches by approximately 80%; when they were administered in combination, twitch potentiation was nearly double that caused by either drug alone. In the presence of nifedipine, halothane increased twitches by less than 30%. Low Ca2+ significantly depressed twitches by approximately 25% but also inhibited halothane's inotropic effect. BAY K 8644 augmented caffeine potentiation but only at low caffeine concentrations (0.5–2.0 mM). Nifedipine and low Ca2+ failed to inhibit caffeine's inotropic effects. These results suggest that halothane potentiates twitches via a mechanism that involves or is influenced by extracellular Ca2+.

Effects of Calcium-free Solution, Calcium Antagonists, and the Calcium Agonist BAY K 8644 on Mechanical Responses of Skeletal Muscle from Patients Susceptible to Malignant Hyperthermia

1991 ◽  
Vol 75 (3) ◽  
pp. 413-419 ◽  
Author(s):  
Pascal J. Adnet ◽  
Renée M. Krivosic-Horber ◽  
Monique M. Adamantidis ◽  
Hugo Reyford ◽  
Corinne Cordonnier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Malignant Hyperthermia ◽  
Calcium Antagonists ◽  
Bay K 8644 ◽  
Free Solution ◽  
Mechanical Responses

Reduced Ca2+-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum at low pH

1992 ◽  
Vol 70 (6) ◽  
pp. 926-930 ◽  
Author(s):  
Jay H. Williams ◽  
Christopher W. Ward
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Ions ◽  
Rate Constants ◽  
Low Ph ◽  
Fiber Bundles ◽  
Hydrogen Ions ◽  
Muscle Calcium ◽  
Caffeine Contractures

The purpose of this investigation was to determine the effects of reduced pH on Ca2+-induced Ca2+ release (CICR) from skeletal muscle sarcoplasmic reticulum (SR). Frog semitendinosus fiber bundles (1–3/bundle) were chemically skinned via saponin treatment (50 μg/mL, 20 min), which removes the sarcolemma and leaves the SR functional. The SR was first depleted of Ca2+ then loaded for 2 min at pCa (log free Ca2+ concentration) 6.6. CICR was then evoked by exposing the fibers to pCa 5–7 for 5–60 s. CICR was evoked both in the absence of ATP and Mg2+ and in the presence of β,γ-methyieneadenosine-5′-triphosphate (AMPPCP, a nonhydrolyzable form of ATP) and Mg2+. Ca2+ remaining in the SR was then assayed via caffeine (25 mM) contracture. In all cases, CICR evoked at pH 6.5 resulted in larger caffeine contractures than that evoked at 7.0, suggesting that more Ca2+ was released during CICR at the higher pH. Accordingly, rate constants for CICR were significantly greater at pH 7.0 than at pH 6.5. These results indicate that reduced pH depresses CICR from skeletal muscle SR.Key words: sarcoplasmic reticulum, skeletal muscle, calcium ions, hydrogen ions, fatigue.

scholarly journals Internal and external effects of dihydropyridines in the calcium channel of skeletal muscle.

1990 ◽  
Vol 95 (1) ◽  
pp. 1-27 ◽  
Author(s):  
H H Valdivia ◽  
R Coronado
Keyword(s):  
Skeletal Muscle ◽  
Lipid Bilayers ◽  
Radioligand Binding ◽  
Quantitative Agreement ◽  
Bay K 8644 ◽  
Single Channels ◽  
Ca Channel ◽  
Ca Channels ◽  
Receptor Sites ◽  
Internal Side

The agonist effect of the dihydropyridine (DHP) (-)Bay K 8644 and the inhibitory effects of nine antagonist DHPs were studied at a constant membrane potential of 0 mV in Ca channels of skeletal muscle transverse tubules incorporated into planar lipid bilayers. Four phenylalkylamines (verapamil, D600, D575, and D890) and d-cis-diltiazem were also tested. In Ca channels activated by 1 microM Bay K 8644, the antagonists nifedipine, nitrendipine, PN200-110, nimodipine, and pure enantiomer antagonists (+)nimodipine, (-)nimodipine, (+)Bay K 8644, inhibited activity in the concentration range of 10 nM to 10 microM. Effective doses (ED50) were 2 to 10 times higher when HDPs were added to the internal side than when added to the external side. This sidedness arises from different structure-activity relationships for DHPs on both sides of the Ca channel since the ranking potency of DHPs is PN200-110 greater than (-)nimodipine greater than nifedipine approximately S207-180 on the external side while PN200-110 greater than S207-180 greater than nifedipine approximately (-)nimodipine on the internal side. A comparison of ED50's for inhibition of single channels by DHPs added to the external side and ED50's for displacement of [3H]PN200-110 bound to the DHP receptor, revealed a good quantitative agreement. However, internal ED50's of channels were consistently higher than radioligand binding affinities by up to two orders of magnitude. Evidently, Ca channels of skeletal muscle are functionally coupled to two DHP receptor sites on opposite sides of the membrane.

Calcium-dependent resistance to stretch and stress relaxation in resting smooth muscles

1976 ◽  
Vol 231 (5) ◽  
pp. 1501-1508 ◽  
Author(s):  
MJ Siegman ◽  
TM Butler ◽  
SU Mooers ◽  
RE Davies
Keyword(s):  
Stress Relaxation ◽  
Smooth Muscles ◽  
Muscle Length ◽  
Taenia Coli ◽  
Tetraacetic Acid ◽  
Active Tension ◽  
Tension Development ◽  
Calcium Dependent ◽  
Mechanical Responses ◽  
State Force

Mechanical responses to stretch and length-tension relations were examined in rabbit taenia coli, mesenteric vein, aorta, and myometrium and in guinea pig taenia coli made atonic by incubation in Krebs-bicarbonate solution at 20-22 degrees C. When stretched 10% of the length at which maximum active tension is observed (Lo) in 0.5 s, the muscles showed a transient large force (resistance to stretch) that decayed to a new constant level within minutes (stress relaxation). The resistance to stretch decreased markedly in Ca2+-free [disodium ethylene glycolbis-(beta-aminoethylether)-N,N-tetraacetic acid (EGTA)] Krebs but was restored in normal Krebs solution. Calcium removal did not affect the passive length-tension curve. The absence of Ca2+ did not change the steady-state force maintained by the muscle; thus stretch resistance was not due to tone. Blockade of Ca2+ influx associated with electrical activity with 5-[3,4-dimethoxyphenethyl)methylamino]-2-(3,4,5-trimethoxyphenyl-2-isoprop ylvaleronitrile (D-600) and of Ca2+ release from intracellular sites with thymol (1 mM) completely blocked contraction but did not alter the responses to stretch, thus dissociating the responses to stretch from these processes and tension development. The Ca2+-dependent stress relaxation showed a dependence on muscle length similar to that for active tension development. Except at long muscle lengths, where connective tissue markedly affects length-tension relations, most of the "viscoelasticity" of these smooth muscles is dependent on calcium and may be largely due to the straining of crossbridges that are attached, but not generating a net force, in the resting state.

The Effect of Lanthanum on Excitation–Contraction Coupling in Frog Skeletal Muscle

1974 ◽  
Vol 52 (6) ◽  
pp. 1126-1135 ◽  
Author(s):  
D. J. Parry ◽  
A. Kover ◽  
G. B. Frank
Keyword(s):  
Skeletal Muscle ◽  
Action Potential ◽  
Muscle Membrane ◽  
Frog Skeletal Muscle ◽  
Tension Development ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Reduced Rate ◽  
Caffeine Contractures

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.

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