Nitrendipine blocks high potassium contractures but not twitches in rat skeletal muscle

1988 ◽  
Vol 66 (9) ◽  
pp. 1210-1213 ◽  
Author(s):  
G. B. Frank ◽  
L. Konya ◽  
T. Subrahmanyam Sudha
Keyword(s):  
Skeletal Muscle ◽  
Calcium Ions ◽  
Calcium Uptake ◽  
Channel Blocker ◽  
Mechanical Response ◽  
Extracellular Calcium ◽  
The Other ◽  
Rat Skeletal Muscle ◽  
Potassium Depolarization ◽  
High Potassium

The effects of the organic calcium channel blocker nitrendipine was tested on electrically evoked twitches and on potassium depolarization-induced contractures of rat lumbricalis muscles. Nitrendipine (10−7 to 5 × 10−5 M) blocked only the potassium contractures. It was concluded that blocking calcium uptake through the slow voltage-senstitive calcium channels during potassium depolarization blocks the mechanical response of the muscle. Thus extracellular calcium ions are required for the excitation–contraction (E–C) coupling during depolarization contractures. On the other hand, electrically evoked twitches were not affected by nitrendipine; therefore, extracellular calcium ions entering via the slow voltage-sensitive channels are not required for E–C coupling during the twitch.

scholarly journals Does a calmodulin-dependent Ca2+-regulated Mg2+-dependent ATPase contribute to hepatic microsomal calcium uptake?

1987 ◽  
Vol 243 (3) ◽  
pp. 729-737 ◽  
Author(s):  
S Schütze ◽  
H D Söling
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Plasma Membranes ◽  
Calcium Uptake ◽  
Liver Cells ◽  
The Other ◽  
Rat Skeletal Muscle ◽  
True Location ◽  
Parenchymal Liver ◽  
Parenchymal Cells

Solubilization of microsomal proteins followed by calmodulin affinity chromatography resulted in the separation of two distinct Ca2+-Mg2+-ATPases (Ca2+-regulated Mg2+-dependent ATPases), one being insensitive to calmodulin (ATPase-1), the other being stimulated about 5-fold by calmodulin (ATPase-2). ATPase-2 accounts for only 8% of total microsomal Ca2+-Mg2+-ATPase-activity. ATPase-1 and -2 can also be distinguished by different pH optima, different sensitivity towards inhibition by vanadate and LaCl3, and different apparent Mr values of the phosphoenzyme intermediates (115,000 and 150,000 for ATPase-1 and ATPase-2 respectively). ATPase-1 from liver co-migrated with Ca2+-Mg2+-ATPase from rat skeletal-muscle sarcoplasmic reticulum, whereas ATPase-2 from liver co-migrated with calmodulin-dependent Ca2+-Mg2+-ATPase derived from rat skeletal-muscle sarcolemma. After separation of parenchymal and nonparenchymal liver cells, a calmodulin-dependent Ca2+-Mg2+-ATPase of Mr 150,000 was found only in the non-parenchymal cells. The kinetic parameters of ATPase-2 and the similarity of the apparent Mr of its phosphoenzyme intermediate to that of skeletal-muscle sarcolemma Ca2+-Mg2+-ATPase makes it likely that the calmodulin-sensitive Ca2+-Mg2+-ATPase found in rat liver microsomal fractions reflects a contamination with plasma membranes (possibly from non-parenchymal cells) rather than a true location in the endoplasmic reticulum of parenchymal liver cells.

Diazepam reveals different rate-limiting processes in rat skeletal muscle contraction

1987 ◽  
Vol 65 (2) ◽  
pp. 272-273 ◽  
Author(s):  
Michael Chua ◽  
Angela F. Dulhunty
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Binding ◽  
Extensor Digitorum Longus ◽  
Calcium Uptake ◽  
Rat Skeletal Muscle ◽  
Skeletal Muscle Contraction ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Rate Limiting

The action of the tranquilizer diazepam on rat skeletal muscle showed that relaxation of isometric twitches is controlled by different processes in extensor digitorum longus (fast-twitch) and soleus (slow-twitch) muscles. Diazepam caused an increase in the amplitude of twitches in fibres from both muscles but increased the twitch duration only in soleus. The amplitude of fused tetani were reduced in both muscles and the rate of relaxation after the tetanus slowed by as much as 34% when the amplitude of the tetanus was reduced by only 11%. The slower tetanic relaxation indicated that calcium uptake by the sarcoplasmic reticulum was slower than normal in slow- and fast-twitch fibres. We conclude therefore that calcium uptake by the sarcoplasmic reticulum is rate limiting for twitch relaxation in slow-twitch but not fast-twitch fibres and suggest that calcium binding to parvalbumin controls relaxation in the fast fibres.

Evidence for an essential role for calcium in excitation-contraction coupling in skeletal muscle

1964 ◽  
Vol 160 (981) ◽  
pp. 504-512 ◽  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibre ◽  
Calcium Ions ◽  
Essential Role ◽  
Mechanical Response ◽  
Frog Heart ◽  
Muscle Fibres ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Spontaneous Action

The events and processes that link the electrical events which occur at the surface of a muscle fibre with the contractile process that takes place within the fibre, have been a continuing source of interest. Recently attention has been concentrated on the role played by calcium ions in linking these two events. As often happens in physiological investigations, the idea that calcium ions play an essential role in excitation-contraction coupling is not new. As long ago as 1883 Ringer demonstrated that the frog heart fails to contract and remains relaxed when calcium ions are absent from its perfusion fluid. Later it was shown that under this condition the rhythmic spontaneous action potentials of this preparation are still present in an only slightly modified form (Mines 1913). It was known at that time that the depolarization of the muscle fibre membrane is the electrical event responsible for initiating the mechanical response (Biedermann 1896) and although this point has been disputed from time to time, the evidence presently available makes it obvious that this is the case. One explanation of these observations is that the action potential or depolarization permits or promotes the movement of calcium ions from the surface to the interior of the muscle fibre and that these ions then initiate the mechanical response. A working hypothesis of this type was proposed by Sandow (1952). However, until fairly recently the only direct evidence supporting such an hypothesis was the demonstration by Heilbrunn & Wiercinski (1947) that calcium was the only physiologically occurring cation which would cause shortening when injected into bits of skeletal muscle fibres in low concentrations. This effect was later confirmed under more physiological conditions by Niedergerke (1955). Although there is considerable evidence of recent origin showing that calcium ions play an essential role in coupling in smooth and cardiac muscles, for the sake of brevity attention will be concentrated on skeletal muscle in the present discussion.

Defective Membrane Systems in Dystrophic Skeletal Muscle of the UM-X7.1 Strain of Genetically Myopathic Hamster

1975 ◽  
Vol 49 (4) ◽  
pp. 359-368
Author(s):  
N. S. Dhalla ◽  
A. Singh ◽  
S. L. Lee ◽  
M. B. Anand ◽  
A. M. Bernatsky ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Atpase Activity ◽  
Calcium Binding ◽  
Adenosine Triphosphatase ◽  
Calcium Uptake ◽  
Initial Rate ◽  
The Other ◽  
Membrane Systems ◽  
Dystrophic Muscle ◽  
Mitochondrial Calcium Uptake

1. The function of mitochondria, sarcotubular membranes (heavy microsomes), sarcolemma and myofibrils from the hind-leg skeletal muscle of about 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters was examined. 2. The mitochondrial calcium uptake as well as mitochondrial phosphorylation and respiratory rates were lower in 60-day-old myopathic skeletal muscle, unlike 150-day-old myopathic animals, when pyruvate-malate and glutamate-malate were used as substrates. However, mitochondria from 150-day-old myopathic animals showed depressed glutamate-dependent respiratory and phosphorylation rates and succinate-supported initial rate of calcium uptake. 3. The microsomal calcium-uptake, but not calcium-binding, and Ca2+-stimulated adenosine triphosphatase (ATPase) activity of the 150-day-old myopathic skeletal muscle were lower than the control values. Although microsomal calcium-binding, calcium-uptake and ATPase activities of the 60-day-old myopathic muscle were not depressed significantly, the initial rate of calcium uptake was less than the control. 4. The sarcolemmal Ca2+-ATPase, but not Mg2+-ATPase or Na+ +K+-ATPase, activity was higher in 60-day-old myopathic muscle whereas the activities of all these enzymes from 150-day-old myopathic animals were higher than the control. On the other hand, the Na+ +K+-ATPase activities from 60- and 150-day-old myopathic animals were inhibited by ouabain to a lesser extent in comparison with the respective control values. 5. The myofibrillar Ca2+-ATPase and Mg2+-ATPase activities as well as inhibition of Mg2+-ATPase due to Na+ and K+ in myopathic muscle were no different from the control values. 6. The results reported here give further support to the view that different membrane systems of the dystrophic muscle are defective.

scholarly journals Voltage-induced Ca2+ release is supported by junctophilins 1, 2 and 3, and not by junctophilin 4

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Stefano Perni ◽  
Kurt G. Beam
Keyword(s):  
Skeletal Muscle ◽  
Conformational Changes ◽  
Knockout Mice ◽  
Calcium Release ◽  
Calcium Entry ◽  
Extracellular Calcium ◽  
Signaling Proteins ◽  
Potassium Depolarization ◽  
Complementary Approach ◽  
In Cells

In skeletal muscle, depolarization of the plasma membrane (PM) causes conformational changes of the calcium channel CaV1.1, which then activate RYR1 to release calcium from the sarcoplasmic reticulum (SR). Because it does not require extracellular calcium entry, this process is termed voltage-induced calcium release. In skeletal muscle, junctophilins (JPH) 1 and 2 are responsible for forming the SR–PM junctions at which voltage-induced calcium release occurs; structurally similar junctions with different molecular constituents are formed in neurons by JPH3 and JPH4. Studies on mice models demonstrated that JPH1 knockout mice can still perform voltage-induced calcium release, although the complementary approach to verify whether JPH1 alone also supports this release is not easily practicable due to the embryonic lethality of JPH2 knockout mice. In a previous work, we showed that voltage-induced calcium release could be recapitulated in HEK293-derived cells transfected with cDNAs for JPH2 and CaV1.1, β1a, Stac3, and RYR1. Here, we used this reconstitutional approach to test whether JPH1 and the more distantly related JPH3 and JPH4 can also support voltage-induced calcium release in HEK293-derived cells. Our data show that all the four isoforms colocalize with CaV1.1 at ER–PM junctions and that JPH1, JPH2, and JPH3, but not JPH4, cause colocalization of RYR1 with CaV1.1 at the junctions. To test for function, potassium depolarization was applied to cells in which WT CaV1.1 was replaced with the calcium impermeant mutant CaV1.1(N617D) to eliminate extracellular calcium entry. Calcium transients were observed in cells expressing JPH1, JPH2, and JPH3, indicating that these isoforms support voltage-induced calcium release, but not in cells expressing JPH4. Thus, the JPHs seem to act primarily to (1) form ER–PM junctions and (2) recruit the required set of signaling proteins to these junctions; voltage-induced calcium release can be supported by any JPH isoform fulfilling both of these functions.

Skeletal muscle calcium uptake in bacteremic rats

1989 ◽  
Vol 256 (1) ◽  
pp. R201-R206 ◽  
Author(s):  
M. V. Westfall ◽  
M. M. Sayeed
Keyword(s):  
Escherichia Coli ◽  
Skeletal Muscle ◽  
Calcium Uptake ◽  
Rat Skeletal Muscle ◽  
Calcium Blockers ◽  
High K ◽  
Time Required ◽  
Muscle Calcium ◽  
Ca2 Channels ◽  
Stimulation Of

To determine whether cellular Ca2+ regulation is altered in bacteremic rat skeletal muscle, 45Ca2+ uptake was measured in soleus muscles 12 h after an intraperitoneal bacterial (Escherichia coli) injection. Some rats received diltiazem (2.4 mg/kg iv) 10 h after bacterial injection to determine whether calcium blockers could inhibit changes in Ca2+ regulation. Cellular exchangeable Ca2+ was measured in soleus muscles incubated for 5 min to 4 h in Krebs-Ringer bicarbonate (KRB) media (pH 7.4) containing 45Ca2+ (1.5 muCi/ml) and subsequently "washed" in La3+-containing, Ca2+-free KRB media. Bacteremia had no effect on steady-state exchangeable Ca2+, but it significantly reduced the time required to reach half-maximal uptake compared with controls. Diltiazem treatment returned the half-maximal Ca2+ uptake toward control values in bacteremic rat muscles. Depolarization of soleus muscles with high K+ (60 mM) transiently increased Ca2+ uptake in control and bacteremic rat muscles, although the increase was significantly greater (P less than 0.05) in bacteremic rat muscles. The altered skeletal muscle Ca2+ regulation may be due to excessive stimulation of Ca2+ messenger systems, sarcolemmal Ca2+ channels, and/or Ca2+ release from the sarcoplasmic reticulum in response to bacteremia.

Changes in insulin receptor kinase with aging in rat skeletal muscle and liver

1990 ◽  
Vol 259 (1) ◽  
pp. E27-E35
Author(s):  
S. Kono ◽  
H. Kuzuya ◽  
M. Okamoto ◽  
H. Nishimura ◽  
A. Kosaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Wheat Germ ◽  
Kinase Activity ◽  
The Other ◽  
Receptor Kinase ◽  
Rat Skeletal Muscle ◽  
Old Rats ◽  
Insulin Receptor Kinase ◽  
Insulin Receptor Kinase Activity

To see if insulin receptor kinase activity alters with aging, the activity of wheat germ agglutinin-purified receptor preparations from liver and skeletal muscle was compared in 2-, 4-, 10-, and 20-mo-old rats. Basal and insulin-stimulated autophosphorylation of liver insulin receptor and its kinase activities toward histone 2b and poly(Glu4Tyr1) did not alter with aging. On the other hand, the muscle insulin receptor showed different results. Insulin-stimulated increases of autophosphorylation and the kinase activity toward histone 2b above basal were comparable in the four groups. However, insulin-stimulated phosphorylation of poly(Glu4Tyr1) was decreased in 20-mo-old rats compared with 10- and 4-mo-old rats. These results indicate that insulin receptor kinase activity could vary under certain conditions, depending on the substrate used to measure the activity. It is concluded that insulin receptor kinase activity does not change markedly during the process of aging, although subtle changes seem to exist.

Insulin binding and sensitivity in rat skeletal muscle: effect of starvation

1981 ◽  
Vol 240 (2) ◽  
pp. E184-E190 ◽  
Author(s):  
L. J. Brady ◽  
M. N. Goodman ◽  
F. N. Kalish ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Insulin Binding ◽  
The Other ◽  
Rat Skeletal Muscle ◽  
In Vitro Sensitivity

In contrast to adipose tissue and heart, the in vitro sensitivity of skeletal muscle to insulin is enhanced by starvation. To determine the basis for this, insulin binding and its ability to stimulate glucose metabolism were examined in the incubated rat soleus. In solei from 50-g rats, starvation for 48 h enhanced insulin binding by 50-100% at concentrations of 100 ng/ml or less. Starvation also resulted in higher basal and insulin-stimulated rates of glycogen synthesis, glycolysis, and glucose uptake. The enhanced effect of insulin only occurred at concentrations less than 50-75 ng/ml, in keeping with the increased binding of insulin in this concentration range. On the other hand, under conditions in which binding at equilibrium was the same, glucose uptake was still higher in the starved group, suggesting that some postreceptor event may have been more sensitive to insulin. These studies confirm that the in vitro sensitivity of rat skeletal muscle to insulin is enhanced by 48 h of starvation. They suggest that this is due at least partially to an increase in insulin binding at physiological concentrations.

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