Ca2+-Mobility in the Sarcoplasmic Reticulum of Ventricular Myocytes Is Low

Swietach, Pawel; Spitzer, Kenneth W.; Vaughan‐Jones, Richard D.

doi:10.1529/biophysj.108.130385

Cited by 53 publications

(81 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The time constant for the refilling of V SRrl in the HuVEC model is~200 ms, which is in agreement with that previously reported for rabbit (59). It should be noted, however, that the refilling time course and Ca 2þ mobility in the SR varies between different studies (59,60). The recovery time course of local Ca 2þ depletion, the so-called blink, is also variable between different studies (61,62).…”

Section: Verification Of Assuming Jnc and Izsupporting

confidence: 89%

A Human Ventricular Myocyte Model with a Refined Representation of Excitation-Contraction Coupling

Himeno

Asakura

Young

et al. 2015

Biophysical Journal

View full text Add to dashboard Cite

Cardiac Ca(2+)-induced Ca(2+) release (CICR) occurs by a regenerative activation of ryanodine receptors (RyRs) within each Ca(2+)-releasing unit, triggered by the activation of L-type Ca(2+) channels (LCCs). CICR is then terminated, most probably by depletion of Ca(2+) in the junctional sarcoplasmic reticulum (SR). Hinch et al. previously developed a tightly coupled LCC-RyR mathematical model, known as the Hinch model, that enables simulations to deal with a variety of functional states of whole-cell populations of a Ca(2+)-releasing unit using a personal computer. In this study, we developed a membrane excitation-contraction model of the human ventricular myocyte, which we call the human ventricular cell (HuVEC) model. This model is a hybrid of the most recent HuVEC models and the Hinch model. We modified the Hinch model to reproduce the regenerative activation and termination of CICR. In particular, we removed the inactivated RyR state and separated the single step of RyR activation by LCCs into triggering and regenerative steps. More importantly, we included the experimental measurement of a transient rise in Ca(2+) concentrations ([Ca(2+)], 10-15 μM) during CICR in the vicinity of Ca(2+)-releasing sites, and thereby calculated the effects of the local Ca(2+) gradient on CICR as well as membrane excitation. This HuVEC model successfully reconstructed both membrane excitation and key properties of CICR. The time course of CICR evoked by an action potential was accounted for by autonomous changes in an instantaneous equilibrium open probability of couplons. This autonomous time course was driven by a core feedback loop including the pivotal local [Ca(2+)], influenced by a time-dependent decay in the SR Ca(2+) content during CICR.

show abstract

Section: Verification Of Assuming Jnc and Izsupporting

confidence: 89%

A Human Ventricular Myocyte Model with a Refined Representation of Excitation-Contraction Coupling

Himeno

Asakura

Young

et al. 2015

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…On the other hand, low Ca 2+ mobility would facilitate SR emptying by restricting the aforementioned redistribution of Ca 2+ within the SR network. However, studies of the intra-SR diffusion yielded conflicting results with nearly an order of magnitude difference in the apparent diffusion coefficients (8 µm 2 /s [38] vs. 60 µm 2 /s [39,40]). Resolving the precise role of local SR Ca 2+ depletion in termination of Ca 2+ release will require future investigation into Ca 2+ diffusion through the SR network as well as further advances in the techniques for measurement of luminal Ca 2+ in cardiac myocytes.…”

Section: Luminal Ca2+ and Sr Ca2+ Release Terminationmentioning

confidence: 99%

Store-dependent deactivation: Cooling the chain-reaction of myocardial calcium signaling

Radwański

Belevych

Brunello

et al. 2013

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

In heart cells, Ca2+ released from the internal storage unit, the sarcoplasmic reticulum (SR) through ryanodine receptor (RyR2) channels is the predominant determinant of cardiac contractility. Evidence obtained in recent years suggests that SR Ca2+ release is tightly regulated not only by cytosolic Ca2+ but also by intra-store Ca2+ concentration. Specifically, Ca2+-induced Ca2+ release (CICR) that relies on auto-catalytic action of Ca2+ at the cytosolic side of RyR2s is precisely balanced and counteracted by RyR2 deactivation dependent on a reciprocal decrease of Ca2+ at the luminal side of RyR2s. Dysregulation of this inherently unstable Ca2+ signaling is considered to be an underlying cause of triggered arrhythmias, and is associated with genetic and acquired forms of sudden cardiac death. In this article, we present an overview of recent advances in our understanding of the regulatory role luminal Ca2+ plays in Ca2+ handling, with a particular emphasis on the role of Ca2+ release refractoriness in aberrant Ca2+ release. This article is part of a Special Issue entitled “Calcium Signaling in Heart”.

show abstract

“…Localized Ca2+responses IP 3 is a rapidly diffusing messenger and IP 3 R are subject to positive feedback CICR on a single luminally-continuous entity, so how do highly-localized Ca 2+ changes occur? In heart cells, the store is also a continuous network [82] in which Ca 2+ can rapidly redistribute [83,84] and positive feedback CICR occurs at RyR, yet highly localized Ca 2+ release events occur. The highly localized responses arise in specialized domains formed by a junction of the store with the plasmalemma ('peripheral couplings') or the store and transverse (T)-tubules ('Dyads').…”

Section: Methods Used To Investigate Stores May Create the Appearancementioning

confidence: 99%

Calcium Mobilization via Intracellular Ion Channels, Store Organization and Mitochondria in Smooth Muscle

McCarron

Chalmers

Wilson

et al. 2016

Vascular Ion Channels in Physiology and Disease

View full text Add to dashboard Cite

This version is available at https://strathprints.strath.ac.uk/55095/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. Abstract In smooth muscle, Ca 2+ release from the internal store into the cytoplasm occurs via inositol trisphosphate (IP 3 R) and ryanodine receptors (RyR). The internal Ca 2+ stores containing IP 3 R and RyR may be arranged as multiple separate compartments with various IP 3 R and RyR arrangements, or there may be a single structure containing both receptors. The existence of multiple stores is proposed to explain several physiological responses which include the progression of Ca 2+ waves, graded Ca 2+ release from the store and various local responses and sensitivities. We suggest that, rather than multiple stores, a single luminally-continuous store exists in which Ca 2+ is in free diffusional equilibrium throughout. Regulation of Ca 2+ release via IP 3 R and RyR by the local Ca 2+ concentration within the stores explains the apparent existence of multiple stores and physiological processes such as graded Ca 2+ release and Ca 2+ waves. Close positioning of IP 3 R on the store with mitochondria or with receptors on the plasma membrane creates 'IP 3 junctions' to generate local responses on the luminally-continuous store.

show abstract

Ca2+-Mobility in the Sarcoplasmic Reticulum of Ventricular Myocytes Is Low

Cited by 53 publications

References 50 publications

A Human Ventricular Myocyte Model with a Refined Representation of Excitation-Contraction Coupling

A Human Ventricular Myocyte Model with a Refined Representation of Excitation-Contraction Coupling

Store-dependent deactivation: Cooling the chain-reaction of myocardial calcium signaling

Calcium Mobilization via Intracellular Ion Channels, Store Organization and Mitochondria in Smooth Muscle

Contact Info

Product

Resources

About