scholarly journals Calcium buffers and L-type calcium channels as modulators of cardiac subcellular alternans

2019 ◽  
Author(s):  
Yi Ming Lai ◽  
Stephen Coombes ◽  
Rüdiger Thul
Keyword(s):  
Membrane Potential ◽  
Sarcoplasmic Reticulum ◽  
Calcium Channels ◽  
Calcium Release ◽  
Computational Study ◽  
Calcium Signalling ◽  
Severe Condition ◽  
Calcium Diffusion ◽  
Calcium Buffers ◽  
The Impact

AbstractIn cardiac myocytes, calcium cycling links the dynamics of the membrane potential to the activation of the contractile filaments. Perturbations of the calcium signalling toolkit have been demonstrated to disrupt this connection and lead to numerous pathologies including cardiac alternans. This rhythm disturbance is characterised by alternations in the membrane potential and the intracellular calcium concentration, which in turn can lead to sudden cardiac death. In the present computational study, we make further inroads into understanding this severe condition by investigating the impact of calcium buffers and L-type calcium channels on the formation of subcellular calcium alternans when calcium diffusion in the sarcoplasmic reticulum is strong. Through numerical simulations of a two dimensional network of calcium release units, we show that increasing calcium entry is proarrhythmogenic and that this is modulated by the calcium-dependent inactivation of the L-type calcium channel. We also find that while calcium buffers can exert a stabilising force and abolish subcellular Ca2+alternans, they can significantly shape the spatial patterning of subcellular calcium alternans. Taken together, our results demonstrate that subcellular calcium alternans can emerge via various routes and that calcium diffusion in the sarcoplasmic reticulum critically determines their spatial patterns.

Analytically depicting the calcium diffusion for Alzheimer’s affected cell

2018 ◽  
Vol 11 (07) ◽  
pp. 1850088 ◽  
Author(s):  
Devanshi D. Dave ◽  
Brajesh Kumar Jha
Keyword(s):  
Mathematical Model ◽  
Calcium Ions ◽  
Complex Structure ◽  
Calcium Signalling ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Calcium Diffusion ◽  
The Impact ◽  
The Brain ◽  
Very High

Brain is the most complex structure of the human body. The processes going inside the brain and the mechanisms behind it have been unrevealed up to certain extent only. Out of the various physiological phenomena carried out by the brain, calcium signalling can be considered as one of the most important. Calcium being a second messenger plays an important role in transformation of various information. In view of above, an attempt has been made here to study calcium signalling in presence of buffers, i.e. one kind of proteins and endoplasmic reticulum (ER), which is also known as store house of the cell. Being the store house of the cell, it has very high amount of calcium, whereas buffers decrease the level of free calcium ions by binding calcium ions to it. A two-dimensional mathematical model has been developed to see the impact of these parameters on cytosolic calcium concentration. This mathematical model is solved analytically using Laplace transforms and similarity transforms. The simulations are carried out using MATLAB. It is observed that the impact of buffer and ER is significant on calcium signalling. The obtained results are interpreted with the Alzheimeric condition of the nerve cells.

scholarly journals The ryanodine receptor/junctional channel complex is regulated by growth factors in a myogenic cell line.

1991 ◽  
Vol 114 (2) ◽  
pp. 303-312 ◽  
Author(s):  
A R Marks ◽  
M B Taubman ◽  
A Saito ◽  
Y Dai ◽  
S Fleischer
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Channels ◽  
Cell Line ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Contractile Protein ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Receptor Mrnas

The ryanodine receptor/junctional channel complex (JCC) forms the calcium release channel and foot structures of the sarcoplasmic reticulum. The JCC and the dihydropyridine (DHP) receptor in the transverse tubule are two of the major components involved in excitation-contraction (E-C) coupling in skeletal muscle. The DHP receptor is believed to serve as the voltage sensor in E-C coupling. Both the JCC and DHP receptor, as well as many skeletal muscle-specific contractile protein genes, are expressed in the BC3H1 muscle cell line. In the present study, we find that during differentiation of BC3H1 cells, induced by mitogen withdrawal, induction of the JCC and DHP receptor mRNAs is temporally similar to that of the skeletal muscle contractile protein genes alpha-tropomyosin and alpha-actin. Our data suggest that there is coordinate regulation of both the contractile protein genes (which have been studied in detail previously) and the genes encoding the calcium channels involved in E-C coupling. Induction of both calcium channels is accompanied by profound changes in BC3H1 cell morphology including the development of many components of mature skeletal muscle cells, despite lack of myoblast fusion. Visualized by electron microscopy, the JCC appears as "foot structures" located in the dyad junction between the plasmalemma and the sarcoplasmic reticulum of the BC3H1 cells. Development of foot structures is concomitant with JCC mRNA expression. Expression of the JCC and DHP receptor mRNAs and formation of the foot structures are inhibited specifically by fibroblast growth factor.

Contribution of a voltage-sensitive calcium release mechanism to contraction in cardiac ventricular myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. H155-H170 ◽  
Author(s):  
Susan E. Howlett ◽  
Jie-Quan Zhu ◽  
Gregory R. Ferrier
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Ventricular Myocytes ◽  
Cardiac Contraction ◽  
Release Mechanism ◽  
Steady State Inactivation ◽  
Slope Factor ◽  
The Relationship

The contribution of a voltage-sensitive release mechanism (VSRM) for sarcoplasmic reticulum (SR) Ca2+ to contraction was investigated in voltage-clamped ventricular myocytes at 37°C. Na+ current was blocked with lidocaine. The VSRM exhibited steady-state inactivation (half-inactivation voltage: −47.6 mV; slope factor: 4.37 mV). When the VSRM was inactivated, contraction-voltage relationships were proportional to L-type Ca2+current ( I Ca-L). When the VSRM was available, the relationship was sigmoidal, with contractions independent of voltage positive to −20 mV. VSRM and I Ca-Lcontractions could be separated by activation-inactivation properties. VSRM contractions were extremely sensitive to ryanodine, thapsigargin, and conditioning protocols to reduce SR Ca2+ load. I Ca-Lcontractions were less sensitive. When both VSRM and I Ca-L were available, sigmoidal contraction-voltage relationships became bell-shaped with protocols to reduce SR Ca2+ load. Myocytes demonstrated restitution of contraction that was slower than restitution of I Ca-L. Restitution was a property of the VSRM. Thus activation and recovery of the VSRM are important in coupling cardiac contraction to membrane potential, SR Ca2+ load, and activation interval.

scholarly journals Cardiac Alternans Occurs through the Synergy of Voltage- and Calcium-Dependent Mechanisms

Membranes ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 794
Author(s):  
Minh Tuan Hoang-Trong ◽  
Aman Ullah ◽  
William Jonathan Lederer ◽  
Mohsin Saleet Jafri
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Channels ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Cellular Level ◽  
Open Probability ◽  
Calcium Dependent ◽  
Cardiac Alternans ◽  
Rapid Pacing ◽  
Dependent Mechanism

Cardiac alternans is characterized by alternating weak and strong beats of the heart. This signaling at the cellular level may appear as alternating long and short action potentials (APs) that occur in synchrony with alternating large and small calcium transients, respectively. Previous studies have suggested that alternans manifests itself through either a voltage dependent mechanism based upon action potential restitution or as a calcium dependent mechanism based on refractoriness of calcium release. We use a novel model of cardiac excitation-contraction (EC) coupling in the rat ventricular myocyte that includes 20,000 calcium release units (CRU) each with 49 ryanodine receptors (RyR2s) and 7 L-type calcium channels that are all stochastically gated. The model suggests that at the cellular level in the case of alternans produced by rapid pacing, the mechanism requires a synergy of voltage- and calcium-dependent mechanisms. The rapid pacing reduces AP duration and magnitude reducing the number of L-type calcium channels activating individual CRUs during each AP and thus increases the population of CRUs that can be recruited stochastically. Elevated myoplasmic and sarcoplasmic reticulum (SR) calcium, [Ca2+]myo and [Ca2+]SR respectively, increases ryanodine receptor open probability (Po) according to our model used in this simulation and this increased the probability of activating additional CRUs. A CRU that opens in one beat is less likely to open the subsequent beat due to refractoriness caused by incomplete refilling of the junctional sarcoplasmic reticulum (jSR). Furthermore, the model includes estimates of changes in Na+ fluxes and [Na+]i and thus provides insight into how changes in electrical activity, [Na+]i and sodium-calcium exchanger activity can modulate alternans. The model thus tracks critical elements that can account for rate-dependent changes in [Na+]i and [Ca2+]myo and how they contribute to the generation of Ca2+ signaling alternans in the heart.

Fluorescent potentiometric dyes for membrane-potential imaging

1994 ◽  
Vol 52 ◽  
pp. 166-167
Author(s):  
Leslie M. Loew
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Quantitative Imaging ◽  
Optical Recording ◽  
Biological Processes ◽  
Major Focus ◽  
The Past ◽  
Excitable Systems ◽  
Major Application ◽  
The Impact

A major application of potentiometric dyes has been the multisite optical recording of electrical activity in excitable systems. After being championed by L.B. Cohen and his colleagues for the past 20 years, the impact of this technology is rapidly being felt and is spreading to an increasing number of neuroscience laboratories. A second class of experiments involves using dyes to image membrane potential distributions in single cells by digital imaging microscopy - a major focus of this lab. These studies usually do not require the temporal resolution of multisite optical recording, being primarily focussed on slow cell biological processes, and therefore can achieve much higher spatial resolution. We have developed 2 methods for quantitative imaging of membrane potential. One method uses dual wavelength imaging of membrane-staining dyes and the other uses quantitative 3D imaging of a fluorescent lipophilic cation; the dyes used in each case were synthesized for this purpose in this laboratory.

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