Increase in calcium sensitivity of cardiac myofibrils contributes to the cardiotonic action of sulmazole

1988 ◽  
Vol 37 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Jacques C.A. van Meel ◽  
Rainer Zimmermann ◽  
Willi Diederen ◽  
Erland Erdman ◽  
Ulrike Mrwa
1990 ◽  
Vol 259 (2) ◽  
pp. R204-R209 ◽  
Author(s):  
E. D. Stevens ◽  
R. E. Godt

Contractile performance decreases with a decrease in temperature and increases with an increase in pH. In general, a decrease in ambient temperature is associated with an increase of the pH of the intracellular and extracellular fluids of ectotherms. Thus the concomitant increase in pH will to some extent counteract the effect of the decrease in temperature. We review the magnitude of this effect and show that it is modest for force (24%) but is small or negligible for speed or for variables involving time. Experiments with skinned fibers yield similar results to those with intact fibers. We argue that one important effect of the concomitant increase in pH is that it causes an increase in calcium sensitivity and that there may be a considerable metabolic saving associated with releasing less calcium at lower temperatures.


2010 ◽  
Vol 426 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Jofre Ferrer-Dalmau ◽  
Asier González ◽  
Maria Platara ◽  
Clara Navarrete ◽  
José L. Martínez ◽  
...  

Maintenance of cation homoeostasis is a key process for any living organism. Specific mutations in Glc7, the essential catalytic subunit of yeast protein phosphatase 1, result in salt and alkaline pH sensitivity, suggesting a role for this protein in cation homoeostasis. We screened a collection of Glc7 regulatory subunit mutants for altered tolerance to diverse cations (sodium, lithium and calcium) and alkaline pH. Among 18 candidates, only deletion of REF2 (RNA end formation 2) yielded increased sensitivity to these conditions, as well as to diverse organic toxic cations. The Ref2F374A mutation, which renders it unable to bind Glc7, did not rescue the salt-related phenotypes of the ref2 strain, suggesting that Ref2 function in cation homoeostasis is mediated by Glc7. The ref2 deletion mutant displays a marked decrease in lithium efflux, which can be explained by the inability of these cells to fully induce the Na+-ATPase ENA1 gene. The effect of lack of Ref2 is additive to that of blockage of the calcineurin pathway and might disrupt multiple mechanisms controlling ENA1 expression. ref2 cells display a striking defect in vacuolar morphogenesis, which probably accounts for the increased calcium levels observed under standard growth conditions and the strong calcium sensitivity of this mutant. Remarkably, the evidence collected indicates that the role of Ref2 in cation homoeostasis may be unrelated to its previously identified function in the formation of mRNA via the APT (for associated with Pta1) complex.


2002 ◽  
Vol 27 (1) ◽  
pp. 42-55 ◽  
Author(s):  
Brian R. Macintosh ◽  
Dilson E. Rassier

Fatigue and potentiation are two forms of force modulation. A general definition of fatigue is "a circumstance where less than the anticipated contractile response is obtained." Fatigue is associated with depressed Ca2+ release and possibly decreased Ca2+ sensitivity. Potentiation results from increased Ca2+ sensitivity due to regulatory light chain phosphorylation. Muscle fatigue and potentiation can coexist, making it difficult to quantify these processes. With repetitive 10 Hz stimulation, the developed tension first increases, then decreases. Is fatigue present when developed tension first begins to decrease or when it falls below the developed tension of the first response? Intermittent incompletely fused tetanic contractions for which peak developed tension first decreases, then increases, is another unusual example of fatigue. A third example is when twitch contractions following a tetanic contraction decrease to a level below the pretetanic twitch amplitude, indicating that fatigue may have been coexistent with posttetanic potentiation. These observations illustrate the complexity of detecting fatigue, based on the simple, but commonly accepted definition presented above. Care must be taken in interpreting "before vs. after" contractile responses. Even when the contraction amplitude is greater than the initial response, there is no guarantee that mechanisms associated with fatigue are not present. Key words: calcium sensitivity, staircase, posttetanic potentiation, myosin light chains, skeletal muscle


1962 ◽  
Vol 18 (1) ◽  
pp. 167-174 ◽  
Author(s):  
J. L. BROADBENT ◽  
K. BOWDEN
Keyword(s):  

2010 ◽  
Vol 49 (3) ◽  
pp. 449-458 ◽  
Author(s):  
Eun-Jeong Lee ◽  
Jun Peng ◽  
Michael Radke ◽  
Michael Gotthardt ◽  
Henk L Granzier

2014 ◽  
Vol 307 (10) ◽  
pp. H1487-H1496 ◽  
Author(s):  
Sander Land ◽  
Steven A. Niederer ◽  
William E. Louch ◽  
Åsmund T. Røe ◽  
Jan Magnus Aronsen ◽  
...  

In Takotsubo cardiomyopathy, the left ventricle shows apical ballooning combined with basal hypercontractility. Both clinical observations in humans and recent experimental work on isolated rat ventricular myocytes suggest the dominant mechanisms of this syndrome are related to acute catecholamine overload. However, relating observed differences in single cells to the capacity of such alterations to result in the extreme changes in ventricular shape seen in Takotsubo syndrome is difficult. By using a computational model of the rat left ventricle, we investigate which mechanisms can give rise to the typical shape of the ventricle observed in this syndrome. Three potential dominant mechanisms related to effects of β-adrenergic stimulation were considered: apical-basal variation of calcium transients due to differences in L-type and sarco(endo)plasmic reticulum Ca2+-ATPase activation, apical-basal variation of calcium sensitivity due to differences in troponin I phosphorylation, and apical-basal variation in maximal active tension due to, e.g., the negative inotropic effects of p38 MAPK. Furthermore, we investigated the interaction of these spatial variations in the presence of a failing Frank-Starling mechanism. We conclude that a large portion of the apex needs to be affected by severe changes in calcium regulation or contractile function to result in apical ballooning, and smooth linear variation from apex to base is unlikely to result in the typical ventricular shape observed in this syndrome. A failing Frank-Starling mechanism significantly increases apical ballooning at end systole and may be an important additional factor underpinning Takotsubo syndrome.


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