scholarly journals Cyclic nucleotide regulation of the contractile proteins in mammalian cardiac muscle.

1980 ◽  
Vol 75 (3) ◽  
pp. 283-295 ◽  
Author(s):  
G B McClellan ◽  
S Winegrad
Keyword(s):  
Cardiac Muscle ◽  
Inotropic Effect ◽  
Bathing Solution ◽  
Contractile System ◽  
Nonionic Detergent ◽  
Nucleotide Regulation ◽  
Inhibitory Subunit Of Troponin ◽  
Concentration Changes ◽  
Significant Interference ◽  
Ca Sensitivity

The contractile system of rat cardiac muscle that has been made hyperpermeable by soaking the tissue in EGTA (McClellan and Winegrad. 1978. J. Gen. Physiol. 72:737-764) can be probed directly with Ca buffer from the bathing solution without significant interference from either sarcoplasmic reticulum or mitochondria on the Ca concentration. Changes in Ca-activated force are due therefore to changes in the properties of the contractile system itself and not to regulation of Ca concentration. The addition of cAMP, cGMP, and GTP, guanylyl imidodiphosphate (GMP-PNP), or epinephrine to the bath does not alter maximum Ca-activated force, but when these drugs are added with 1% nonionic detergent to the bath, contractility increases by as much as 180%. An inhibitor of phosphodiesterase must be present for the inotropic effect of cAMP but not cGMP, GTP, GMP-PNP, or epinephrine. The inotropic response to cAMP is independent of the Ca sensitivity of the contractile system, but guanine nucleotides enhance contractility only when Ca sensitivity is not high. The inotropic effect of epinephrine is inhibited to a large extent by cGMP but not by GMP-PNP. These data can be explained by a model in which contractility is enhanced by a cAMP-regulated phosphorylation that can be controlled through the beta-receptor adenylate cyclase complex in the sarcolemma. The regulation involves two reactions, one a phosphorylation and a second that occurs in the presence of detergent. Phosphorylation of neither the myosin light chain nor the inhibitory subunit of troponin appears to be involved in this mechanism for regulating contractility.

scholarly journals Calcium sensitivity of the contractile system and phosphorylation of troponin in hyperpermeable cardiac cells.

1980 ◽  
Vol 75 (3) ◽  
pp. 271-282 ◽  
Author(s):  
L Mope ◽  
G B McClellan ◽  
S Winegrad
Keyword(s):  
Cyclic Nucleotides ◽  
Polyacrylamide Gel Electrophoresis ◽  
Calcium Sensitivity ◽  
Ventricular Myocardium ◽  
Cardiac Cells ◽  
Contractile System ◽  
Maximum Activation ◽  
Nonionic Detergent ◽  
Inhibitory Subunit Of Troponin ◽  
Ca Sensitivity

Bundles of cells from rat right ventricular myocardium were made "hyperpermeable" by an overnight soak in 10 mM EGTA (McClellan and Winegrad. 1978. J. Gen. Physiol. 72:737-764). In this preparation the cytoplasmic concentration of Ca++ and ATP could be controlled while sarcolemmal receptors and enzymes were retained. The Ca sensitivity of the tissues (as indicated by the pCa for 50% maximum activation) was altered to different extents in the presence of [32Pgamma]ATP by treatment with cyclic nucleotides, catecholamines, or a low concentration of nonionic detergent. The proteins of the tissue were then isolated by SDS-polyacrylamide gel electrophoresis, and the identity of 32P-labeled proteins was determined. The Ca sensitivity is inversely related to the relative amount of 32P incorporated into the inhibitory subunit of troponin (TNI). Extrapolation of the relation to the lowest Ca sensitivity observed gives a stoichiometry of about 0.8 mol PO4 per mol TNI. These results support the hypothesis that Ca sensitivity of cardiac myofibrils is regulated by a phosphrylation of TNI that is stimulated by cyclic AMP (cAMP) and inhibited by cGMP.

scholarly journals The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle.

1978 ◽  
Vol 72 (6) ◽  
pp. 737-764 ◽  
Author(s):  
G B McClellan ◽  
S Winegrad
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Regulatory System ◽  
Calcium Sensitivity ◽  
Cardiac Cells ◽  
General Shape ◽  
Contractile System ◽  
Ventricular Cells ◽  
Phosphate Donor ◽  
Nonionic Detergent ◽  
Ca Sensitivity

Treatment of rat ventricular cells with 10 mM EGTA makes the sarcolemma highly permeable to small ions and molecules without removing its restriction of the diffusion of larger molecules or inactivating all of its enzymatic functions. These hyperpermeable cardiac cells have been used to study the regulation of the range of concentration of Ca over which activation of the contractile proteins occurs (Ca sensitivity). The Ca sensitivity can varied from three- to sixfold without any significant alteration in the general shape of the relation between force and Ca concentrations. Although cyclic nucleotides in concentrations of 10(-9) to 10(-5) M do not influence Ca sensitivity, in the presence of a phosphodiesterase inhibitor, cGMP increases and cAMP decreases Ca sensitivity. Treatment of the hyperpermeable cells with a nonionic detergent raises Ca sensitivity as does removal of the phosphate donor by complete substitution of CTP for ATP. These data indicate that Ca sensitivity is probably modulated by a cAMP-dependent phosphorylation that decreases Ca sensitivity. The sarcolemma is required for this reaction to take place. The effect of this reaction is antagonized by a cGMP-dependent reaction occurring inside the cell. Studies involving the perfusion of the heart with and without epinephrine before the exposure to EGTA indicate that epinephrine can regulate this system of control of Ca sensitivity. The functional considerations of this regulatory system are discussed.

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)

Effects of ischemia on sarcoplasmic reticulum and contractile myofilament activity in human myocardium

1993 ◽  
Vol 265 (4) ◽  
pp. H1334-H1341 ◽  
Author(s):  
G. B. Luciani ◽  
A. D'Agnolo ◽  
A. Mazzucco ◽  
V. Gallucci ◽  
G. Salviati
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Isometric Tension ◽  
Hill Coefficient ◽  
Calmodulin Antagonist ◽  
Contractile System ◽  
Cardiac Fiber ◽  
And Control

The effects of global ischemia on the contractile system and on sarcoplasmic reticulum (SR) function were studied by measuring the isometric tension and the SR Ca2+ release activity of chemically skinned cardiac fiber preparations from seven patients undergoing open-heart surgery. Ten minutes of ischemia caused 1) a decrease in the myofilament sensitivity to Ca2+ (expected Ca2+ concentration giving half-maximal tension; from 0.69 +/- 0.04 to 1.38 +/- 0.06 microM, n = 7) and in the cooperativity index (Hill coefficient; from 2.61 +/- 0.45 to 0.92 +/- 0.15, n = 7), 2) a decrease in myosin light chain phosphorylation, and 3) a 300% increase in the threshold caffeine concentration for SR Ca2+ efflux channel activation, with a 30% reduction in the rate of Ca2+ release by caffeine at threshold concentrations and a 23% reduction in the rate of release by 20 mM caffeine. After preincubation with 5 microM trifluoperazine, a calmodulin antagonist, the caffeine threshold of ischemic and control cardiac muscle became comparable. Most changes were reversed by reperfusion, while the caffeine threshold was still two times greater than control. These results indicate that ischemia caused alterations of the cardiac muscle contractile apparatus and the SR that were reversed only after reperfusion.

Positive inotropic effect of Streptococcus faecalis in isolated cardiac muscle

1994 ◽  
Vol 267 (6) ◽  
pp. H2450-H2461 ◽  
Author(s):  
I. E. Schoemaker ◽  
S. U. Sys ◽  
L. J. Andries ◽  
J. M. Meyers ◽  
S. R. Pattyn ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Positive Inotropic Effect ◽  
Mechanical Performance ◽  
Bacterial Colonization ◽  
Ringer Solution ◽  
Inotropic Effect ◽  
Maximal Velocity ◽  
Acute Effects ◽  
Before And After ◽  
Isometric Twitch

Infective endocarditis is caused by bacterial colonization of the endocardium. Because endocardium modulates mechanical performance of subjacent myocardium, we studied acute effects of bacteria on isolated cardiac muscle and on the functional role of the endocardium. Bacteria, grown in broth at 37 degrees C, were added at increasing concentrations (10(2) to 10(6) bacteria/ml) to cat papillary muscles in Krebs-Ringer solution (1.25 mM Ca2+, 35 degrees C). The endocardial surface was damaged by exposing muscles to a stream of dry air for 30 s. Streptococcus (Enterococcus) faecalis induced significant increases in total peak isometric twitch tension (TT) and maximal velocity of unloaded shortening (Vmax) and significant decreases in time to TT (TtTT) and time to half isometric twitch tension decline (RT 1/2), both before and after removal of endocardial endothelium. This response could also be elicited with bacterial filtrate, after boiling the filtrate or after extracting the polysaccharides from it with KIO4. Increasing Ca2+ concentrations progressively reduced the response to the filtrate. Propranolol slightly, although not significantly, diminished the effects on TT and Vmax while abolishing the effects on TtTT and on RT 1/2. By contrast, Streptococcus bovis and Staphylococcus aureus did not affect TT or Vmax but induced a slight but significant decrease in TtTT at the highest concentration of bacteria. Accordingly, the filtrate of Strep. faecalis induces a positive inotropic effect. The active component is neither a protein nor a polysaccharide, and its effect may be partly beta-adrenoceptor mediated. Strep. bovis and Staph. aureus have negligible acute effects on contractility.

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 BAPTA on force and Ca2+ transient during isometric contraction of frog muscle fibers

1998 ◽  
Vol 275 (2) ◽  
pp. C375-C381 ◽  
Author(s):  
Y.-B. Sun ◽  
C. Caputo ◽  
K. A. P. Edman
Keyword(s):  
Mechanical Performance ◽  
Muscle Fibers ◽  
Frog Muscle ◽  
Clear Correlation ◽  
Bathing Solution ◽  
Control Value ◽  
Contractile System ◽  
Intracellular Ca ◽  
Cross Bridges ◽  
Reduced State

The effects of 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA) on force and intracellular Ca2+ transient were studied during isometric twitches and tetanuses in single frog muscle fibers. BAPTA was added to the bathing solution in its permeant AM form (50 and 100 μM). There was no clear correlation between the changes in force and the changes in Ca2+ transient. Thus during twitch stimulation BAPTA did not suppress the Ca2+ transient until the force had been reduced to <50% of its control value. At the same time, the peak myoplasmic free Ca2+concentration reached during tetanic stimulation was markedly increased, whereas the force was slightly reduced by BAPTA. The effects of BAPTA were not duplicated by using another Ca2+ chelator, EGTA, indicating that BAPTA may act differently as a Ca2+ chelator. Stiffness measurements suggest that the decrease in mechanical performance in the presence of BAPTA is attributable to a reduced number of active cross bridges. The results could mean that BAPTA, under the conditions used, inhibits the binding of Ca2+ to troponin C resulting in a reduced state of activation of the contractile system.

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