Modeling Mechanical-Electrical Transduction in the Heart

Sachs, Frederick

doi:10.1007/978-1-4613-8425-0_18

Cited by 32 publications

(22 citation statements)

References 41 publications

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“…This gives a reversal potential of -5 mV and a conductance of 900 pS at 0 mV. This mimics the activation of 1 % of total membrane SACs with a single-channel conductance of 25 pS at a channel density of 0 3 ,tm 2 (Sachs, 1994 (Gannier et al , 1996.…”

Section: Stretching Of Single Myocytesmentioning

confidence: 69%

Gadolinium blocks the delayed rectifier potassium current in isolated guinea‐pig ventricular myocytes

Hongo¹,

Pascarel²,

Cazorla³

et al. 1997

Experimental Physiology

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SUMMARYThe effect of Gd3+ on the delayed rectifier potassium current (IK) in single guinea-pig ventricular myocytes was tested using whole-cell patch-clamp techniques. It was found that Gdd3+ blocked 70 % of the IK tail current at a concentration of 100 4M. The EC50 was 24 uM. Action potential durations were, however, reduced, consistent with a predominant effect on depolarizing L-type Ca2+ current (VCa,L). In the presence of 5 ,UM nifedipine Gd3+ prolonged the action potential. Using carbon fibres to stretch cells we observed that 1O /M Gd3+ was not effective in reducing a large stretch-activated increase in resting calcium. Modelling studies using the OXSOFT HEART program suggest that this lack of response is influenced by blockade of repolarizing current but is best reproduced by additional blockade of Ca2+ extrusion via the Na'-Ca2' exchanger. When Gd3+ is used as a blocker of stretch-activated channels its actions upon both lCa,L and IK must therefore be accounted for.

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Section: Stretching Of Single Myocytesmentioning

confidence: 69%

Gadolinium blocks the delayed rectifier potassium current in isolated guinea‐pig ventricular myocytes

Hongo¹,

Pascarel²,

Cazorla³

et al. 1997

Experimental Physiology

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“…Detailed models of stretch activated currents (SACs) can be found in the literature (see for instance [14,17,19]). However, since our approach is firstly qualitative and interested in physical mechanisms, we will instead of well accepted but rather complex models use a very simple and generic description of the SACs, inspired by [22] and also used in [7,20].…”

Section: A Governing Equationsmentioning

confidence: 99%

“…This phenomenon has been studied for a long time, both experimentally and theoretically (see for instance [7,[11][12][13][14][15][16][17][18][19][20][21][22]) and it is now well accepted that MEF can elicit spontaneous oscillatory behavior in muscle fibers. In the present work, we propose is a theoretical and numerical analysis of such oscillations.…”

Section: Introductionmentioning

confidence: 99%

Temperature, geometry, and bifurcations in the numerical modeling of the cardiac mechano-electric feedback

Collet

Bragard

Dauby

2017

Chaos: An Interdisciplinary Journal of Nonlinear Science

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This article characterizes the cardiac autonomous electrical activity induced by the mechanical deformations in the cardiac tissue through the mechano-electric feedback (MEF). A simplified and qualitative model is used to describe the system and we also account for temperature effects. The analysis emphasizes a very rich dynamics for the system, with periodic solutions, alternans, chaotic behaviors, etc. The possibility of self-sustained oscillations is analyzed in detail, particularly in terms of the values of important parameters such as the dimension of the system and the importance of the stretch-activated currents. It is also shown that high temperatures notably increase the parameters ranges for which self-sustained oscillations are observed and that several attractors can appear, depending on the location of the initial excitation of the system. Finally, the instability mechanisms by which the periodic solutions are destabilized have been studied by a Floquet analysis, which has revealed period-doubling phenomena and transient intermittencies.

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“…Depending on the characteristics of the SACs, their activation in isolation has been predicted to shorten the guinea-pig ventricular action potential (Sachs, 1994;Kohl et al 1998), or cause a 'cross-over' (Kohl et al 1998;Reimer et al 1998). Han et al (2001) recently suggested that activation of SACs might shorten the APD, primarily through modulation of [Na + ] i .…”

Section: Journal Of Physiologymentioning

confidence: 99%

Streptomycin and intracellular calcium modulate the response of single guinea‐pig ventricular myocytes to axial stretch

Belus

White

2003

The Journal of Physiology

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Isolation of guinea-pig ventricular myocytesGuinea-pigs (weight approximately 300 g) were killed by cervical dislocation following stunning; all procedures conformed with the UK Animals (Scientific Procedures) Act 1986. Left ventricular myocytes were isolated using methods based on those of Frampton et al. (1991). Briefly, hearts were removed and mounted on a Langendorff apparatus and perfused with a Hepes-based isolation solution of the following composition (mM): NaCl 130; KCl 5.4; NaH 2 PO 4 0.4; MgCl 2 .6H 2 O 1.4; CaCl 2 1.8; Hepes 10; glucose 10; taurine 20; creatine 10; with 1 % bovine serum albumin (pH 7.3) to clear blood from the coronary circulation. Perfusion was then continued with Ca 2+ -free isolation solution Streptomycin and intracellular calcium modulate the response of single guinea-pig ventricular myocytes to axial stretch Alexandra Belus and Ed White School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UKWe tested the hypothesis that both stretch-activated channels (SACs) and intracellular calcium ([Ca 2+ ] i ) are important in the electrical response of single guinea-pig ventricular myocytes to axial stretch. Myocytes were attached to carbon fibre transducers and stretched, sarcomere length increased by approximately 9 %, and there was a prolongation of the action potential duration. Streptomycin, a blocker of SACs, had no effect upon the shortening, [Ca 2+ ] i transients or action potentials of electrically stimulated, unstretched myocytes, at a concentration of 50 mM, but at 40 mM, prevented any stretch-induced increase in action potential duration. Under action potential clamp, stretch elicited a current with a linear current-voltage relationship that was inward at membrane potentials negative to its reversal potential of _30 mV, in 10 of 24 cells tested, and was consistent with the activation of non-specific, cationic SACs. This current was not seen in any stretched cells that were exposed to 40 mM streptomycin. However, exposure of cells to 5 mM BAPTA-AM, in order to reduce [ Journal of Physiology(1.8 mM CaCl 2 replaced with 0.1 mM EGTA) for 4 min, followed by 5 min perfusion with isolation solution containing 50 mM Ca 2+ , 1 mg ml _1 collagenase (type II; Worthington Biochemical Corporation, NJ, USA) and 0.1 mg ml _1 protease (type XIV; Sigma Chemical Co.). The left ventricle was then separated from the rest of the heart, minced, and gently shaken at 37°C in the collagenase-containing isolation solution. Cells were filtered from this solution at 5 min intervals and resuspended in isolation solution containing 1.8 mM Ca 2+ .To ] i were measured simultaneously. A video image of the cell was monitored using an edge detection system (Crescent Electronics, UT, USA) and the change in cell length following stimulation was used as our measure of contractility. Cells were loaded with the Ca 2+ -sensitive fluorescent indicator fura-2 AM (Molecular Probes, OR, USA) by incubation for 10 min at 22-24° C in 1.8 mM Ca 2+ isolation solution containing 3-5 mM fura-2 AM. The ratio of fl...

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Modeling Mechanical-Electrical Transduction in the Heart

Cited by 32 publications

References 41 publications

Gadolinium blocks the delayed rectifier potassium current in isolated guinea‐pig ventricular myocytes

Gadolinium blocks the delayed rectifier potassium current in isolated guinea‐pig ventricular myocytes

Temperature, geometry, and bifurcations in the numerical modeling of the cardiac mechano-electric feedback

Streptomycin and intracellular calcium modulate the response of single guinea‐pig ventricular myocytes to axial stretch

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