scholarly journals SLC8 family of sodium/calcium exchangers (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Jules Hancox
Keyword(s):  
Calcium Influx ◽  
Sodium Concentration ◽  
Sodium Ion ◽  
Reverse Direction ◽  
Intracellular Loop ◽  
Sodium Potassium ◽  
Sodium Efflux ◽  
Sodium Calcium ◽  
Extracellular Sodium ◽  
Cellular Stimulation

The sodium/calcium exchangers (NCX) use the extracellular sodium concentration to facilitate the extrusion of calcium out of the cell. Alongside the plasma membrane Ca2+-ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA), as well as the sodium/potassium/calcium exchangers (NKCX, SLC24 family), NCX allow recovery of intracellular calcium back to basal levels after cellular stimulation. When intracellular sodium ion levels rise, for example, following depolarisation, these transporters can operate in the reverse direction to allow calcium influx and sodium efflux, as an electrogenic mechanism. Structural modelling suggests the presence of 9 TM segments, with a large intracellular loop between the fifth and sixth TM segments.

scholarly journals SLC8 family of sodium/calcium exchangers in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Jules Hancox
Keyword(s):  
Calcium Influx ◽  
Sodium Concentration ◽  
Sodium Ion ◽  
Reverse Direction ◽  
Intracellular Loop ◽  
Sodium Potassium ◽  
Sodium Efflux ◽  
Sodium Calcium ◽  
Extracellular Sodium ◽  
Cellular Stimulation

The sodium/calcium exchangers (NCX) use the extracellular sodium concentration to facilitate the extrusion of calcium out of the cell. Alongside the plasma membrane Ca2+-ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA), as well as the sodium/potassium/calcium exchangers (NKCX, SLC24 family), NCX allow recovery of intracellular calcium back to basal levels after cellular stimulation. When intracellular sodium ion levels rise, for example, following depolarisation, these transporters can operate in the reverse direction to allow calcium influx and sodium efflux, as an electrogenic mechanism. Structural modelling suggests the presence of 9 TM segments, with a large intracellular loop between the fifth and sixth TM segments [1].

EFFECT OF REDUCED EXTRACELLULAR SODIUM CONCENTRATION ON THE FUNCTION OF ADRENAL ZONA GLOMERULOSA: STUDIES ON ISOLATED GLOMERULOSA CELLS FROM THE RAT

1981 ◽  
Vol 89 (3) ◽  
pp. 417-421 ◽  
Author(s):  
P. ENYEDI ◽  
A. SPÄT
Keyword(s):  
Angiotensin Ii ◽  
Sodium Concentration ◽  
Zona Glomerulosa ◽  
Sodium Ion ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Extracellular Sodium

Aldosterone production by isolated adrenal glomerulosa cells from the rat was estimated in the presence of varying concentrations of sodium ion. The reduction of sodium concentration by 5–20 mmol/l, with or without osmotic changes, did not influence the rate of aldosterone production. Aldosterone response to angiotensin II was not modified by varying the sodium concentration.

The change from symmetry to asymmetry of a sodium transport system in red cell membranes

1985 ◽  
Vol 223 (1233) ◽  
pp. 449-457 ◽  
Keyword(s):  
Sodium Concentration ◽  
Tracer Studies ◽  
Chloride Medium ◽  
Sodium Influx ◽  
Nitrate Medium ◽  
Sodium Efflux ◽  
External Potassium ◽  
Red Cell Membranes ◽  
Stimulation Of ◽  
Human Red Cells

A study has been made with human red cells of sodium movements that are sensitive to the drug furosemide. The aim was to see if furosemide-sensitive movements that are symmetrical (exchange) became asymmetrical (net transport) on replacement of chloride with nitrate as the major external anion. Cells were incubated for 4 h at 37 °C with 140 mm sodium, and chloride or nitrate as the principal anion. Under a variety of conditions (presence and absence of ouabain or furosemide, or both) the cell sodium concentration was always higher when chloride was replaced with nitrate. The cells became leakier to sodium. Tracer studies indicated that, in contrast to the results in chloride medium, the decrease in sodium influx was greater than the fall in efflux when furosemide was added to cells in nitrate medium. The results confirm that the sensitivity of sodium efflux to furosemide depended on chloride. However, influx showed a different sensitivity in that furosemide still inhibited in cells incubated in nitrate medium. The stimulation of sodium influx with nitrate medium was independent of external potassium (10–50 mm) and the furosemide-sensitive influx was also constant. It is concluded that symmetrical transmembrane sodium movements with cells in chloride medium became downhill asymmetrical in nitrate medium, giving a net gain of cell sodium that was insensitive to ouabain and sensitive to furosemide. The drug thus partly retarded the gain of cell sodium that otherwise occurred in the somewhat leaky cells.

Hypernatremia and Intercalated Disc Edema Synergistically Exacerbate Long QT Syndrome Type 3 Phenotype

2021 ◽  
Author(s):  
Xiaobo Wu ◽  
Gregory S. Hoeker ◽  
Grace Blair ◽  
David Ryan King ◽  
Robert G. Gourdie ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Concentration ◽  
Syndrome Type ◽  
Intercalated Disc ◽  
Long Qt ◽  
Disc Edema ◽  
Cardiac Edema ◽  
Qt Syndrome ◽  
Extracellular Sodium ◽  
Type 3

Background: Cardiac voltage-gated sodium channel gain-of-function prolongs repolarization in the Long-QT Syndrome Type 3 (LQT3). Previous studies suggest that narrowing the perinexus within the intercalated disc, leading to rapid sodium depletion, attenuates LQT3-associated action potential duration (APD) prolongation. However, it remains unknown whether extracellular sodium concentration modulates APD prolongation during sodium channel gain-of-function. We hypothesized that elevated extracellular sodium concentration and widened perinexus synergistically prolong APD in LQT3. Methods and Results: LQT3 was induced with anemone toxin type II (ATXII) in Langendorff-perfused guinea pig hearts (n=20). Sodium concentration was increased from 145 to 160 mM. Perinexal expansion was induced with mannitol or the sodium channel β1-subunit adhesion domain antagonist (βadp1). Epicardial ventricular action potentials were optically mapped. Individual and combined effects of varying clefts and sodium concentrations were simulated in a computational model. With ATXII, both mannitol and βadp1 significantly widened the perinexus and prolonged APD, respectively. The elevated sodium concentration alone significantly prolonged APD as well. Importantly, the combination of elevated sodium concentration and perinexal widening synergistically prolonged APD. Computational modeling results were consistent with animal experiments. Conclusions: Concurrently elevating extracellular sodium and increasing intercalated disc edema prolongs repolarization more than the individual interventions alone in the LQT3. This synergistic effect suggests an important clinical implication that hypernatremia in the presence of cardiac edema can markedly increase LQT3-associated APD prolongation. Therefore, this is the first study to provide evidence of a tractable and effective strategy to mitigate LQT3 phenotype by managing patient sodium levels and preventing cardiac edema.

The role of transmembrane sodium gradient in rabbit ileal smooth muscle: Utilization of harmaline

1985 ◽  
Vol 5 (8) ◽  
pp. 667-671 ◽  
Author(s):  
M. S. Suleiman
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Sodium Concentration ◽  
Exchange Mechanism ◽  
Dependent Manner ◽  
Sodium Gradient ◽  
Extracellular Sodium ◽  
Dose Dependent

Decreasing extracellular sodium concentration was found to produce a contractile response of rabbit ileal smooth muscle. As the concentration decreases, the amplitude of contraction increases, thus producing a dose-dependent curve. Harmaline, a competitor for sodium, was found to inhibit the sodium gradient-dependent contractions in a dose-dependent manner. The results are interpreted as harmaline inhibiting a Na–Ca exchange mechanism present in ileal smooth muscle.

scholarly journals Model of skeletal muscle cramp and its reversal

2020 ◽  
Author(s):  
Kazuyo Tasaki ◽  
Penelope J. Noble ◽  
Alan Garny ◽  
Paul R. Shorten ◽  
Nima Afshar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Regulatory Networks ◽  
Calcium Influx ◽  
Muscle Cramp ◽  
Extracellular Potassium ◽  
Extended Model ◽  
Calcium Efflux ◽  
Sodium Calcium ◽  
Calcium Exchange ◽  
Increased Blood Flow

In an accompanying paper [2], we developed the Shorten [3] model of skeletal muscle by incorporating equations such as surface calcium fluxes. In further research in this paper, we succeeded in reproducing muscle cramp, as well as its prevention and reversal, by investigating muscle contraction and cramp, in which calcium regulatory networks are involved, using the extended model in comparison with the original model. Incorporation of data from a traditional medicine from root extracts of paeony and licorice and one of its pure chemicals was modeled. The sensitivity analysis of the extended model shows the robustness of the calcium regulatory networks. Muscle cramp, in the extended model, requires calcium influx via the L-type calcium channel and it will not occur without calcium influx. Reduced calcium influx can delay or prevent cramp. Increased interstitial potassium is implicated in developing and maintaining cramp. Mechanism of reversal of cramp requires wash-out of extracellular potassium via increased blood flow, followed by calcium efflux via sodium-calcium exchange. This paper shows the first successful quantitative electrophysiological and mechanical model of cramp and of its reversal.

scholarly journals Model of skeletal muscle cramp and its reversal

2020 ◽  
Author(s):  
Kazuyo Tasaki ◽  
Denis Noble ◽  
Penelope J. Noble ◽  
Paul R. Shorten ◽  
Alan Garny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Regulatory Networks ◽  
Calcium Influx ◽  
Muscle Cramp ◽  
Extracellular Potassium ◽  
Extended Model ◽  
Calcium Efflux ◽  
Sodium Calcium ◽  
Calcium Exchange ◽  
Increased Blood Flow

In an accompanying paper [2], we developed the Shorten [3] model of skeletal muscle by incorporating equations such as surface calcium fluxes. In further research in this paper, we succeeded in reproducing muscle cramp, as well as its prevention and reversal, by investigating muscle contraction and cramp, in which calcium regulatory networks are involved, using the extended model in comparison with the original model. Incorporation of data from a traditional medicine from root extracts of paeony and licorice and one of its pure chemicals was modeled. The sensitivity analysis of the extended model shows the robustness of the calcium regulatory networks. Muscle cramp, in the extended model, requires calcium influx via the L-type calcium channel and it will not occur without calcium influx. Reduced calcium influx can delay or prevent cramp. Increased interstitial potassium is implicated in developing and maintaining cramp. Mechanism of reversal of cramp requires wash-out of extracellular potassium via increased blood flow, followed by calcium efflux via sodium-calcium exchange. This paper shows the first successful quantitative electrophysiological and mechanical model of cramp and of its reversal.

scholarly journals Model of skeletal muscle cramp and its reversal

2020 ◽  
Author(s):  
Kazuyo Tasaki ◽  
Penelope J. Noble ◽  
Alan Garny ◽  
Paul R. Shorten ◽  
Nima Afshar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Regulatory Networks ◽  
Calcium Influx ◽  
Muscle Cramp ◽  
Extracellular Potassium ◽  
Extended Model ◽  
Calcium Efflux ◽  
Sodium Calcium ◽  
Calcium Exchange ◽  
Increased Blood Flow

In an accompanying paper [2], we developed the Shorten [3] model of skeletal muscle by incorporating equations such as surface calcium fluxes. In further research in this paper, we succeeded in reproducing muscle cramp, as well as its prevention and reversal, by investigating muscle contraction and cramp, in which calcium regulatory networks are involved, using the extended model in comparison with the original model. Incorporation of data from a traditional medicine from root extracts of paeony and licorice and one of its pure chemicals was modeled. The sensitivity analysis of the extended model shows the robustness of the calcium regulatory networks. Muscle cramp, in the extended model, requires calcium influx via the L-type calcium channel and it will not occur without calcium influx. Reduced calcium influx can delay or prevent cramp. Increased interstitial potassium is implicated in developing and maintaining cramp. Mechanism of reversal of cramp requires wash-out of extracellular potassium via increased blood flow, followed by calcium efflux via sodium-calcium exchange. This paper shows the first successful quantitative electrophysiological and mechanical model of cramp and of its reversal.

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