Abstract
In the heart, Na+ is a key modulator of the action potential, Ca2+ homeostasis, energetics, and contractility. Because Na+ currents and cotransport fluxes depend on the Na+ concentration in the submembrane region, it is necessary to accurately estimate the submembrane Na+ concentration ([Na+]sm). Current methods using Na+-sensitive fluorescent indicators or Na+ -sensitive electrodes cannot measure [Na+]sm. However, electrophysiology methods are ideal for measuring [Na+]sm. In this article, we develop patch-clamp protocols and experimental conditions to determine the upper bound of [Na+]sm at the peak of action potential and its lower bound at the resting state. During the cardiac cycle, the value of [Na+]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+]sm value to ∼9 mM; 2) at 2 Hz pacing frequency, [Na+]sm is bounded between 9 mM at resting state and 11.5 mM; and 3) the cells can maintain [Na+]sm to the above values, despite changes in the pipette Na+ concentration, showing autoregulation of Na+ in beating cardiomyocytes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1304-1315 |
| Number of pages | 12 |
| Journal | Biophysical Journal |
| Volume | 111 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 20 2016 |
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ASJC Scopus subject areas
- Biophysics
Cite this
Electrophysiological Determination of Submembrane Na+ Concentration in Cardiac Myocytes. / Hegyi, Bence; Bányász, Tamás; Shannon, Thomas R.; Chen-Izu, Ye; Izu, Leighton T.
In: Biophysical Journal, Vol. 111, No. 6, 20.09.2016, p. 1304-1315.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Electrophysiological Determination of Submembrane Na+ Concentration in Cardiac Myocytes
AU - Hegyi, Bence
AU - Bányász, Tamás
AU - Shannon, Thomas R.
AU - Chen-Izu, Ye
AU - Izu, Leighton T
PY - 2016/9/20
Y1 - 2016/9/20
N2 - In the heart, Na+ is a key modulator of the action potential, Ca2+ homeostasis, energetics, and contractility. Because Na+ currents and cotransport fluxes depend on the Na+ concentration in the submembrane region, it is necessary to accurately estimate the submembrane Na+ concentration ([Na+]sm). Current methods using Na+-sensitive fluorescent indicators or Na+ -sensitive electrodes cannot measure [Na+]sm. However, electrophysiology methods are ideal for measuring [Na+]sm. In this article, we develop patch-clamp protocols and experimental conditions to determine the upper bound of [Na+]sm at the peak of action potential and its lower bound at the resting state. During the cardiac cycle, the value of [Na+]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+]sm value to ∼9 mM; 2) at 2 Hz pacing frequency, [Na+]sm is bounded between 9 mM at resting state and 11.5 mM; and 3) the cells can maintain [Na+]sm to the above values, despite changes in the pipette Na+ concentration, showing autoregulation of Na+ in beating cardiomyocytes.
AB - In the heart, Na+ is a key modulator of the action potential, Ca2+ homeostasis, energetics, and contractility. Because Na+ currents and cotransport fluxes depend on the Na+ concentration in the submembrane region, it is necessary to accurately estimate the submembrane Na+ concentration ([Na+]sm). Current methods using Na+-sensitive fluorescent indicators or Na+ -sensitive electrodes cannot measure [Na+]sm. However, electrophysiology methods are ideal for measuring [Na+]sm. In this article, we develop patch-clamp protocols and experimental conditions to determine the upper bound of [Na+]sm at the peak of action potential and its lower bound at the resting state. During the cardiac cycle, the value of [Na+]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+]sm value to ∼9 mM; 2) at 2 Hz pacing frequency, [Na+]sm is bounded between 9 mM at resting state and 11.5 mM; and 3) the cells can maintain [Na+]sm to the above values, despite changes in the pipette Na+ concentration, showing autoregulation of Na+ in beating cardiomyocytes.
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U2 - 10.1016/j.bpj.2016.08.008
DO - 10.1016/j.bpj.2016.08.008
M3 - Article
VL - 111
SP - 1304
EP - 1315
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 6
ER -