Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle.

Many features of the sequence of action potentials produced by repeated stimulation of a patch of cardiac muscle can be modeled by a 1D mapping, but not the full behavior included in the restitution portrait. Specifically, recent experiments have found that (i) the dynamic and S1-S2 restitution curves are different (rate dependence) and (ii) the approach to steady state, which requires many action potentials (accommodation), occurs along a curve distinct from either restitution curve. Neither behavior can be produced by a 1D mapping. To address these shortcomings, ad hoc 2D mappings, where the second variable is a "memory" variable, have been proposed; these models exhibit qualitative features of the relevant behavior, but a quantitative fit is not possible. In this paper we introduce a new 2D mapping and determine a set of parameters for it that gives a quantitatively accurate description of the full restitution portrait measured from a bullfrog ventricle. The mapping can be derived as an asymptotic limit of an idealized ionic model in which a generalized concentration acts as a memory variable. This ionic basis clarifies how the present model differs from previous models. The ionic basis also provides the foundation for more extensive cardiac modeling: e.g., constructing a PDE model that may be used to study the effect of memory on propagation. The fitting procedure for the mapping is straightforward and can easily be applied to obtain a mathematical model for data from other experiments, including experiments on different species.

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“…Thus, according to (6), only a small fraction of the ions in the cell are pumped out over the course of one action potential.…”

Section: Mapping Modelsmentioning

confidence: 99%

An Ionically Based Mapping Model with Memory for Cardiac Restitution

et al. 2007

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“…The value of the resting intracellular sodium activity in guinea-pig myocytes has been measured at 7 mm (Rodrigo & Chapman, 1990) and is known to increase with heart rate (Cohen, Fozzard & Sheu, 1982) and on exposure to cardiac glycosides or on removal of divalent cations from the bathing fluid, conditions where a shortening of the action potential also occurs (Chapman & Tunstall, 1986;Rodrigo, 1990 (Rodrigo, 1990). Secondly, block of the KNa current with the non-specific agent R56865 (Luk & Carmeliet, 1990;Rodrigo & Chapman, 1990) reduces the loss of K+ during an ischaemic insult (Mittani & Shattock, 1992) and the shortening of the action potential, but not the inotropic effects of strophanthidin in isolated guinea-pig ventricular myocytes (G. C. Rodrigo & R. A. Chapman, unpublished data).…”

Section: Physiological and Pathophysiological Significancementioning

confidence: 99%

Kinetic properties of unitary Na+‐dependent K+ channels in inside‐out patches from isolated guinea‐pig ventricular myocytes.

Mistry¹,

Tripathi²,

Chapman³

1997

The Journal of Physiology

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1. Single Nae-activated K+ channels (KNa) were investigated by means of the inside-out patch clamp technique in ventricular myocytes isolated from the guinea-pig heart.2. Nae-activated K+ channels were observed at very low density (<9 % of patches Distributions of burst duration, between burst duration and openings within bursts were best described by the sum of two exponentials. Lowering [Na+]i decreased the burst duration and the duration of openings within burst. 6. These observations show that the Na+-activated K+ channel from guinea-pig ventricular myocytes has complex gating and bursting behaviour.Of the wide variety of potassium channels that are found in cell membranes, several show a high unit conductance of between 100 and 200 pS. A channel of this type activated by Nae (KNa) at the intracellular surface has been identified in both neuronal and myocardial cells at the whole-cell and single-channel level

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“…Na þ -sensitive fluorescent indicators have been used to measure the bulk Na þ concentration, but because the fluorescence signal from the bulk cytoplasm vastly overwhelms that from the submembrane volume, Na þ -sensitive fluorescent indicators cannot measure [Na þ ] sm . Na þ -sensitive electrodes and electron-probe microanalysis can, in principle, measure the submembrane Na þ concentration but there are large uncertainties in the spatial position of the sampled region (5). On the other hand, electrophysiological measurements based on whole-cell patch-clamp methods are ideal for measuring submembrane ionic concentrations, because the current is determined by the submembrane ionic milieu.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological Determination of Submembrane Na + Concentration in Cardiac Myocytes

Hegyi

Bányász

Shannon

et al. 2016

Biophysical Journal

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In the heart, Na þ is a key modulator of the action potential, Ca 2þ homeostasis, energetics, and contractility. Because Na þ currents and cotransport fluxes depend on the Na þ concentration in the submembrane region, it is necessary to accurately estimate the submembrane Na þ concentration ([Na þ ] sm ). Current methods using Na þ -sensitive fluorescent indicators or Na þ -sensitive electrodes cannot measure [Na þ ] sm . However, electrophysiology methods are ideal for measuring [Na þ ] sm . In this article, we develop patch-clamp protocols and experimental conditions to determine the upper bound of [Na þ ] sm at the peak of action potential and its lower bound at the resting state. During the cardiac cycle, the value of [Na þ ] sm is constrained within these bounds. We conducted experiments in rabbit ventricular myocytes at body temperature and found that 1) at a low pacing frequency of 0.5 Hz, the upper and lower bounds converge at 9 mM, constraining the [Na þ ] sm value to~9 mM; 2) at 2 Hz pacing frequency, [Na þ ] sm is bounded between 9 mM at resting state and 11.5 mM; and 3) the cells can maintain [Na þ ] sm to the above values, despite changes in the pipette Na þ concentration, showing autoregulation of Na þ in beating cardiomyocytes.

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Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle.

Cited by 259 publications

References 60 publications

An Ionically Based Mapping Model with Memory for Cardiac Restitution

An Ionically Based Mapping Model with Memory for Cardiac Restitution

Kinetic properties of unitary Na+‐dependent K+ channels in inside‐out patches from isolated guinea‐pig ventricular myocytes.

Electrophysiological Determination of Submembrane Na + Concentration in Cardiac Myocytes

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