The role of luminal Ca regulation in Ca signaling refractoriness and cardiac arrhythmogenesis

Simultaneous measurements were made of crayfish muscle Ca2+ currents (ICa) and the intracellular Ca2+ transients they elicit due to Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR). Ca2+ concentration ([Ca2+]) elevations produced by Ca2+ entry via ICa were much more effective in triggering CICR than were ongoing release or homogeneous elevations of Ca2+ produced by photolysis of caged Ca2+. This suggests that [Ca2+] gradients exist when Ca2+ is elevated by ICa and that, during Ca2+ entry, [Ca2+] at the activation site of the release channels must be much greater than spatially averaged [Ca2+] reported by the indicator. Analysis of voltage dependencies of ICa inactivation and SR Ca2+ release suggest that both Ca(2+)-dependent processes are controlled by ICa via the nearest T tubule Ca2+ channel rather than by total ICa entry. The contribution of SR Ca2+ release to ICa inactivation studied with a two-pulse protocol was less than predicted if Ca2+ derived from SR Ca2+ release and from T tubule Ca2+ channels have equal access to the Ca2+ binding site controlling ICa inactivation. These results can be explained in terms of a scheme where sites for release activation and ICa inactivation are located in the same junctional gap subdomain, closer to the cytoplasmic mouth of the T tubule Ca2+ channel than to the cytoplasmic mouth of the SR Ca2+ release channels. Such a scheme could provide an explanation for the graded nature and selective control of CICR in this preparation as well as in vertebrate cardiac muscle.

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Role of Calcium Current and Sarcoplasmic Reticulum Calcium Released in Control of Myocardial Contraction in Rat and Rabbit Myocytes

Journal of Molecular and Cellular Cardiology ◽

10.1006/jmcc.1993.1146 ◽

1993 ◽

Vol 25 (11) ◽

pp. 1339-1347 ◽

Cited By ~ 15

Author(s):

S.Y. Wang ◽

L. Winka ◽

G.A. Langer

Keyword(s):

Sarcoplasmic Reticulum ◽

Calcium Current ◽

Myocardial Contraction ◽

Sarcoplasmic Reticulum Calcium

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Modelling sarcoplasmic reticulum calcium ATPase and its regulation in cardiac myocytes

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2008.0304 ◽

2009 ◽

Vol 367 (1896) ◽

pp. 2181-2202 ◽

Cited By ~ 19

Author(s):

Jussi T. Koivumäki ◽

Jouni Takalo ◽

Topi Korhonen ◽

Pasi Tavi ◽

Matti Weckström

Keyword(s):

Sarcoplasmic Reticulum ◽

Large Scale ◽

Cardiac Myocyte ◽

Model Complexity ◽

Transport Mechanisms ◽

Physiological Properties ◽

Theoretical Considerations ◽

Sarcoplasmic Reticulum Calcium ◽

Modelling Approach

When developing large-scale mathematical models of physiology, some reduction in complexity is necessarily required to maintain computational efficiency. A prime example of such an intricate cell is the cardiac myocyte. For the predictive power of the cardiomyocyte models, it is vital to accurately describe the calcium transport mechanisms, since they essentially link the electrical activation to contractility. The removal of calcium from the cytoplasm takes place mainly by the Na + /Ca 2+ exchanger, and the sarcoplasmic reticulum Ca 2+ ATPase (SERCA). In the present study, we review the properties of SERCA, its frequency-dependent and β -adrenergic regulation, and the approaches of mathematical modelling that have been used to investigate its function. Furthermore, we present novel theoretical considerations that might prove useful for the elucidation of the role of SERCA in cardiac function, achieving a reduction in model complexity, but at the same time retaining the central aspects of its function. Our results indicate that to faithfully predict the physiological properties of SERCA, we should take into account the calcium-buffering effect and reversible function of the pump. This ‘uncomplicated’ modelling approach could be useful to other similar transport mechanisms as well.

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Differences in Ca2+-management between the ventricle of two species of neotropical teleosts: the jeju, Hoplerythrinus unitaeniatus (Spix & Agassiz, 1829), and the acara, Geophagus brasiliensis (Quoy & Gaimard, 1824)

Neotropical Ichthyology ◽

10.1590/s1679-62252009000300015 ◽

2009 ◽

Vol 7 (3) ◽

pp. 471-478 ◽

Cited By ~ 1

Author(s):

Monica Jones Costa ◽

Francisco Tadeu Rantin ◽

Ana Lúcia Kalinin

Keyword(s):

Sarcoplasmic Reticulum ◽

Physiological Role ◽

Stimulation Frequency ◽

Cardiac Sarcoplasmic Reticulum ◽

Heart Frequency ◽

Geophagus Brasiliensis ◽

Hoplerythrinus Unitaeniatus

This study analyzed the physiological role of the cardiac sarcoplasmic reticulum (SR) of two neotropical teleosts, the jeju, Hoplerythrinus unitaeniatus (Erythrinidae), and the acara, Geophagus brasiliensis (Cichlidae). While the in vivo heart frequency (fH - bpm) of acara (79.6 ± 6.6) was higher than that of the jeju (50.3 ± 2.7), the opposite was observed for the ventricular inotropism (Fc - mN/mm²) at 12 bpm (acara = 28.66 ± 1.86 vs. jeju = 36.09 ± 1.67). A 5 min diastolic pause resulted in a strong potentiation of Fc (≅ 90%) of strips from jeju, which was completely abolished by ryanodine. Ryanodine also resulted in a ≅ 20% decrease in the Fc developed by strips from jeju at both subphysiological (12 bpm) and physiological (in vivo) frequencies. However, this effect of ryanodine reducing the Fc from jeju was completely compensated by adrenaline increments (10-9 and 10-6 M). In contrast, strips from acara were irresponsive to ryanodine, irrespective of the stimulation frequency, and increases in adrenaline concentration (to 10-9 and 10-6 M) further increased Fc. These results reinforce the hypothesis of the functionality of the SR as a common trait in neotropical ostariophysian (as jeju), while in acanthopterygians (as acara) it seems to be functional mainly in 'athletic' species.

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