Some Effects of Caffeine and Quinidine on Sarcoplasmic Reticulum of Skeletal and Cardiac Muscle

1973 ◽  
Vol 51 (7) ◽  
pp. 499-503 ◽  
Author(s):  
William R. Thorpe
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Myocardial Contractility ◽  
Gastrocnemius Muscle ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Experimental Conditions

Sarcoplasmic reticulum (SR) was prepared from the gastrocnemius muscle and the heart of freshly killed rabbits. It was found that the skeletal SR actively bound significantly more calcium than did the cardiac SR under the same experimental conditions. The effect of caffeine and quinidine on the release of calcium actively bound by both cardiac and skeletal SR was studied. Quinidine (10−3 M) released 4.1% of the calcium bound by skeletal SR and 27.7% of that bound by cardiac SR. Similarly, caffeine (20 mM) released 10.5% and 34.3% of the calcium bound by skeletal and cardiac SR, respectively. It is suggested that both caffeine and quinidine could produce contracture of skeletal muscle by acting on the SR and that caffeine could stimulate myocardial contractility through its action on the cardiac SR. However, it is unlikely that quinidine exerts its negative inotropic effect on the heart through its calcium releasing action on the cardiac SR.

Effects of 2,3-butanedione monoxime on sarcoplasmic reticulum of saponin-treated rat cardiac muscle

1993 ◽  
Vol 265 (5) ◽  
pp. H1493-H1500 ◽  
Author(s):  
D. S. Steele ◽  
G. L. Smith
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Adenine Nucleotides ◽  
Direct Action ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Butanedione Monoxime ◽  
Net Release

We have studied the effects of 2,3-butanedione monoxime (BDM) on the sarcoplasmic reticulum (SR) of saponin-treated rat cardiac trabeculae. Rapid application of 20 mM caffeine released Ca2+ from the SR, which was detected using the fluorescent Ca2+ indicator indo 1. The amplitude of the caffeine-induced Ca2+ transient was used as an index of the Ca2+ content of the SR before, during, and after exposure to various concentrations of BDM. BDM (1-5 mM) had little effect on caffeine-induced Ca2+ release. At these levels of BDM, force was inhibited predominantly by a direct action of BDM on the myofilaments. However, with higher concentrations (5-30 mM), BDM caused a concentration-dependent decrease in the amount of Ca2+ released from the SR in response to caffeine. This action of BDM may contribute to the negative inotropic effect of the drug in intact cardiac preparations by reducing the amount of Ca2+ available for release during systole. Rapid application of BDM induced a net release of Ca2+ from the SR. Both BDM and caffeine-induced Ca2+ releases were abolished following treatment of the muscle with 10 microM ryanodine. BDM failed to release Ca2+ in the absence of ATP or after substitution of ATP with nonhydrolyzable adenine nucleotides. In contrast, caffeine released Ca2+ in the absence of ATP. The possible involvement of the Ca(2+)-uptake pump in the action of BDM on the SR is discussed.

Interaction of Bupivacaine and Tetracaine with the Sarcoplasmic Reticulum Ca2+Release Channel of Skeletal and Cardiac Muscles 

1999 ◽  
Vol 90 (3) ◽  
pp. 835-843 ◽  
Author(s):  
Hirochika Komai ◽  
Andrew J. Lokuta
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Ryanodine Receptor ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Specific Effect ◽  
Receptor Activity ◽  
Maximal Inhibition ◽  
Release Channel

Background Although various local anesthetics can cause histologic damage to skeletal muscle when injected intramuscularly, bupivacaine appears to have an exceptionally high rate of myotoxicity. Research has suggested that an effect of bupivacaine on sarcoplasmic reticulum Ca2+ release is involved in its myotoxicity, but direct evidence is lacking. Furthermore, it is not known whether the toxicity depends on the unique chemical characteristics of bupivacaine and whether the toxicity is found only in skeletal muscle. Methods The authors studied the effects of bupivacaine and the similarly lipid-soluble local anesthetic, tetracaine, on the Ca2+ release channel-ryanodine receptor of sarcoplasmic reticulum in swine skeletal and cardiac muscle. [3H]Ryanodine binding was used to measure the activity of the Ca2+ release channel-ryanodine receptors in microsomes of both muscles. Results Bupivacaine enhanced (by two times at 5 mM) and inhibited (66% inhibition at 10 mM) [3H]ryanodine binding to skeletal muscle microsomes. In contrast, only inhibitory effects were observed with cardiac microsomes (about 3 mM for half-maximal inhibition). Tetracaine, which inhibits [3H]ryanodine binding to skeletal muscle microsomes, also inhibited [3H]ryanodine binding to cardiac muscle microsomes (half-maximal inhibition at 99 microM). Conclusions Bupivacaine's ability to enhance Ca2+ release channel-ryanodine receptor activity of skeletal muscle sarcoplasmic reticulum most likely contributes to the myotoxicity of this local anesthetic. Thus, the pronounced myotoxicity of bupivacaine may be the result of this specific effect on Ca2+ release channel-ryanodine receptor superimposed on a nonspecific action on lipid bilayers to increase the Ca2+ permeability of sarcoplasmic reticulum membranes, an effect shared by all local anesthetics. The specific action of tetracaine to inhibit Ca2+ release channel-ryanodine receptor activity may in part counterbalance the nonspecific action, resulting in moderate myotoxicity.

A comparison of cyclopiazonic acid and ryanodine effects on cardiac muscle relaxation

1993 ◽  
Vol 265 (4) ◽  
pp. H1364-H1372 ◽  
Author(s):  
N. Pery-Man ◽  
D. Chemla ◽  
C. Coirault ◽  
I. Suard ◽  
B. Riou ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Muscle Relaxation ◽  
Cyclopiazonic Acid ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Control Group ◽  
Total Force ◽  
Uptake Inhibition ◽  
Relaxant Effect ◽  
Isometric Twitch

We investigated cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake. Mechanics of 35 rat papillary muscles were studied after either ryanodine 10(-7) M (n = 11) or cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of shortening (delta L) of the preloaded twitch (delta Lp), and the normalized total force (TF) of the full isometric twitch (TFi). The peak lengthening velocity (Vl) of the preloaded twitch (Vlp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. With the influence of shortening and/or load on relaxation taken into account, analysis of relaxation was performed using 1) Vlp-to-delta Lp and magnitude of -DFi-to-TFi ratios and 2) slopes of the Vl-delta L and magnitude of -DF-TF relationships over the entire continuum of load. Ca(2+)-release inhibition with ryanodine induced a negative inotropic effect and a decrease in Vlp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/S, where Lmax is the initial length at the peak of the length-active tension curve (P < 0.001). The Vlp-to-delta Lp ratio and the slope of the Vl-delta L relationship were preserved, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. Ca(2+)-uptake inhibition with CPA had no inotropic effect but decreased Vlp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Predominant Negative Inotropic Effect of UTP on Dog Cardiac Muscle

1984 ◽  
Vol 35 (3) ◽  
pp. 334-337 ◽  
Author(s):  
Shigetoshi CHIBA ◽  
Miyoharu KOBAYASHI ◽  
Masahiro SHIMOTORI ◽  
Yasuyuki FURUKAWA
Keyword(s):  
Cardiac Muscle ◽  
Negative Inotropic Effect ◽  
Inotropic Effect

Comparative effect of procainamide and lidocaine on myocardial contractility

1969 ◽  
Vol 47 (12) ◽  
pp. 1038-1042 ◽  
Author(s):  
M. Nahas ◽  
J. Lachapelle ◽  
G. M. Tremblay
Keyword(s):  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Inotropic Effect ◽  
Comparative Effect ◽  
Heart Perfusion ◽  
Biphasic Effect ◽  
Therapeutic Doses

The effect of procainamide and lidocaine on myocardial contractility was studied in an isovolumic isolated rat heart perfusion preparation following the Langendorff technique. As a measure of myocardial contractility, the left ventricular intracavitary pressure and maximum dp/dt were determined and were found to be depressed proportionately to the dose of these agents. At the same concentration, lidocaine showed a more negative inotropic effect than procainamide (although the former seems clinically innocuous at therapeutic doses). In addition, procainamide produced in about one-half of the experiments a biphasic effect characterized by a slight transitory positive inotropic effect followed by a negative inotropic effect.

The Anatomy of the Sarcoplasmic Reticulum in Vertebrate Skeletal Muscle: Its Implications for Excitation Contraction Coupling

1982 ◽  
Vol 37 (7-8) ◽  
pp. 665-678 ◽  
Author(s):  
Joachim R. Sommer
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Action Potential ◽  
Cardiac Muscle ◽  
Calcium Release ◽  
Striated Muscle ◽  
Band Region ◽  
Terminal Cisterna ◽  
Transmitter Substance ◽  
Main Components

Abstract The sarcoplasmic reticulum in situ is an intricate tubular network that surrounds the contractile material in striated muscle cells. Its topographical relationship to other intracellular components, especially the myofibrils, is rather rigidly mainiained by a cytoskeleton which enmeshes Z line material and sarcoplasmic reticulum and, ultimately, is anchored at the plasmalemma. As a result, the two main components of the sarcoplasmic reticulum, the junctional SR and the free SR, retain their typical location in the A band region and in the I band region, respectively. The junc­tional SR, which is thought to be the site for calcium storage and release for contraction, is, thus, always well within one micron of the regulatory proteins associated with the actin filaments. The junctional SR, a synonym for terminal cisterna applying to both skeletal and cardiac muscle, is generally held to be involved in the translation of the action potential into calcium release, mainly because of the close topographic apposition between the junctional SR and the plasmalemma, especially in skeletal muscle. This attractive structure-function correlation is challenged by the observation that in bird cardiac muscle 80% of the junctional SR is spacially far removed from plas­malemma, the site of electrical activity. This anomalous topography is not in conflict with the notion that translation of the action potential into calcium release may be accomplished by a dif­fusible transmitter substance, e.g. calcium. Any hypothesis dealing with this problem must ac­ count for the anatomy of the bird heart.

Differential Ca2+ sensitivity of skeletal and cardiac muscle ryanodine receptors in the presence of calmodulin

2000 ◽  
Vol 279 (3) ◽  
pp. C724-C733 ◽  
Author(s):  
Bradley R. Fruen ◽  
Jennifer M. Bardy ◽  
Todd M. Byrem ◽  
Gale M. Strasburg ◽  
Charles F. Louis
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Ryanodine Receptors ◽  
Cross Linking ◽  
Release Channel ◽  
Channel Activation ◽  
Functional Interactions ◽  
Ryr2 Channel

Calmodulin (CaM) activates the skeletal muscle ryanodine receptor Ca2+ release channel (RyR1) in the presence of nanomolar Ca2+ concentrations. However, the role of CaM activation in the mechanisms that control Ca2+ release from the sarcoplasmic reticulum (SR) in skeletal muscle and in the heart remains unclear. In media that contained 100 nM Ca2+, the rate of45Ca2+ release from porcine skeletal muscle SR vesicles was increased approximately threefold in the presence of CaM (1 μM). In contrast, cardiac SR vesicle45Ca2+ release was unaffected by CaM, suggesting that CaM activated the skeletal RyR1 but not the cardiac RyR2 channel isoform. The activation of RyR1 by CaM was associated with an approximately sixfold increase in the Ca2+ sensitivity of [3H]ryanodine binding to skeletal muscle SR, whereas the Ca2+ sensitivity of cardiac SR [3H]ryanodine binding was similar in the absence and presence of CaM. Cross-linking experiments identified both RyR1 and RyR2 as predominant CaM binding proteins in skeletal and cardiac SR, respectively, and [35S]CaM binding determinations further indicated comparable CaM binding to the two isoforms in the presence of micromolar Ca2+. In nanomolar Ca2+, however, the affinity and stoichiometry of RyR2 [35S]CaM binding was reduced compared with that of RyR1. Together, our results indicate that CaM activates RyR1 by increasing the Ca2+ sensitivity of the channel, and further suggest differences in CaM's functional interactions with the RyR1 and RyR2 isoforms that may potentially contribute to differences in the Ca2+ dependence of channel activation in skeletal and cardiac muscle.

Mechanism of the Negative Inotropic Effect of Thiopental in Isolated Ferret Ventricular Myocardium 

1995 ◽  
Vol 82 (2) ◽  
pp. 436-450 ◽  
Author(s):  
Philippe R. Housmans ◽  
Turkan S. Kudsioglu ◽  
Jonathan Bingham
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
Underlying Mechanism ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Force Peak ◽  
Human Ventricular Myocardium ◽  
Negative Inotropic Effects

Background Thiopental's myocardial depressant effects are well known and most likely involve some alteration in intracellular Ca2+ homeostasis. The aim of this study was to investigate the mechanisms of thiopental's negative inotropic effects and its underlying mechanism in isolated ferret ventricular myocardium (which shows physiologic characteristics similar to human ventricular myocardium), and in frog ventricular myocardium, in which Ca2+ ions for myofibrillar activation are derived almost entirely from transsarcolemmal influx. Methods The authors analyzed the effects of thiopental after beta-adrenoceptor blockade on variables of contractility and relaxation, and on the free intracellular Ca2+ transient detected with the Ca(2+)-regulated photoprotein aequorin. Thiopental's effects also were evaluated in ferret right ventricular papillary muscles in which the sarcoplasmic reticulum (SR) function was impaired by ryanodine and in frog ventricular strips with little or no SR function. Results At concentration &gt; or = 10(-4) M, which is in the high range of the clinically encountered free plasma thiopental concentrations, thiopental decreased contractility and the amplitude of the intracellular Ca2+ transient. At equal peak force, peak aequorin luminescence in 10(-4) M thiopental and [Ca2+]0 &gt; 2.25 mM was slightly smaller than that in control conditions at [Ca2+]o = 2.25 mM. This indicates that thiopental causes a small increase in myofibrillar Ca2+ sensitivity. After inactivation of sarcoplasmic reticulum Ca2+ release with 10(-6) M ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca2+ influx, thiopental caused a further decrease in contractility and in the amplitude of the intracellular Ca2+ transient, and thiopental's relative negative inotropic effect was not different from that in control muscles not exposed to ryanodine. Thiopental, &gt; or = 10(-4) M, decreased contractility in frog ventricular myocardium. Conclusions These findings indicate that the direct negative inotropic effect of thiopental results from a decrease in intracellular Ca2+ availability. At least part of thiopental's action is caused by inhibition of transsarcolemmal Ca2+ influx. These effects become apparent at concentrations routinely present during intravenous induction with thiopental.

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