Kinetics, stoichiometry and role of the Na–Ca exchange mechanism in isolated cardiac myocytes

  title={Kinetics, stoichiometry and role of the Na–Ca exchange mechanism in isolated cardiac myocytes},
  author={Lynn M. Crespo and Christopher James Grantham and Mark B. Cannell},
COMPELLING evidence has existed for more than a decade for a sodium/calcium (Na–Ca) exchange mechanism in the surface membrane of mammalian heart muscle cells1–3 which exchanges about three sodium ions for each calcium ion4–6. Although it is known that cardiac muscle contraction is regulated by a transient increase in intracellular calcium ([Ca2+]i) triggered by the action potential7, the contribution of the Na–Ca exchanger to the [Ca2+]i transient and to calcium extrusion during rest is… 

Sodium/calcium exchange regulates cytoplasmic calcium in smooth muscle

The results establish that a Na+/Ca2+ exchanger exists in smooth muscle and argue that it can regulate [Ca2-] at physiological Ca2+ concentrations.

Contribution of Sodium‐Calcium Exchange to Calcium Regulation in Cardiac Muscle a

  • M. Cannell
  • Biology
    Annals of the New York Academy of Sciences
  • 1991
The existence of a sodium-calcium (Na-Ca) exchange mechanism in the surface membrane of cardiac cells has been appreciated for more than a decade and it is now clear that current generated by the exchanger will contribute to the time-course of the action potential.

Species Differences and the Role of Sodium‐Calcium Exchange in Cardiac Muscle Relaxation a

  • D. Bers
  • Biology
    Annals of the New York Academy of Sciences
  • 1991
This work has shown that during normal relaxation in rabbit, guinea-pig, and rat ventricular muscle, the Na-Ca exchange system competes with the SR Ca pump, with the former being responsible for about 20-30% of the Ca removal from the cytoplasm.

Ca transport during contraction and relaxation in mammalian ventricular muscle

  • D. Bers
  • Biology
    Basic Research in Cardiology
  • 2004
Using tissue cultured neonatal rat ventricular myocytes, the effect of chronic arrest or stimulation with phorbol esters (to stimulate protein kinase C) and Verapamil-induced arrest increased the SR Ca-ATPase at the level of mRNA, protein expression and functional ability to lower [Ca]i in intact cells, and Conversely, stimulation or protein kinases C reduced SRCa-ATpase at all three of these levels.

Molecular operations of the sodium–calcium exchanger revealed by conformation currents

The properties of these components provide evidence that the Na–Ca exchanger protein undergoes two consecutive membrane-crossing molecular transitions that each move charge, and that there are at least 250 exchangers per µm2 turning over up to 2,500 times per second.

Kinetics of [Ca]i decline in cardiac myocytes depend on peak [Ca]i.

It is demonstrated that the observed decline in apparent tau with increasing peak [Ca]i is entirely expected on theoretical grounds and over a wide range of characteristics for Ca transport and binding.

Processes that remove calcium from the cytoplasm during excitation‐contraction coupling in intact rat heart cells.

It is concluded that transport of Ca2+ by mitochondria and the surface membrane Ca(2+)‐pumping ATPase would be negligible over the time course of a single [Ca2+]i transient, and the major factors determining the removal of cytoplasmic free Ca2+.

Na‐Ca Exchange and Ca Fluxes during Contraction and Relaxation in Mammalian Ventricular Muscle a

Evaluated dynamic interaction of cellular Ca transport systems during the normal cardiac contraction-relaxation cycle shows the SR Ca-ATPase and Na-Ca exchange are clearly the most important, quantitatively; however, the relative roles vary in a species-dependent manner.

Sodium‐Calcium Exchange in Aortic Myocytes and Renal Epithelial Cells

A combination of experimental approaches is essential for distinguishing changes in cytosolic free Ca2+ that are caused by CaZ+ influx via the Na+-Ca2+ exchanger from the [Ca2-Ii changes due to release of stored Caz+ evoked by triggering the Na-sensitive receptor].

Role of Reverse‐Mode Na+‐Ca2+ Exchange in Excitation‐Contraction Coupling in the Heart a

The results suggest that depolarization-induced Na+ influx through Na+ channels can trigger SR Ca2+ release in cardiac myocytes by activating Ca2- influx via reverse-mode Na(+)-Ca2+ exchange.



Sodium/Calcium Exchange and the Control of Contractility in Cardiac Muscle and Vascular Smooth Muscle

  • M. Blaustein
  • Biology
    Journal of cardiovascular pharmacology
  • 1988
In both cardiac muscle and VSM, the exchanger biases the level of [Ca2+], and thereby controls the amount of Ca2+ stored in the sarcoplasmic reticulum and the amount available for release when the cells are activated.

Extrusion of calcium from rod outer segments is driven by both sodium and potassium gradients

The exchange stoichiometry is 4 Na+:l Ca2+1 K+ and it is proposed that the exchange should be renamed the Na:Ca, K exchange due to the ability of changes in external K+ concentration to perturb the equilibrium level of [Ca2+]i indicates that K+ is co-transported with calcium.

Identification of sodium‐calcium exchange current in single ventricular cells of guinea‐pig.

The Na‐Ca exchange current was investigated in single ventricular cells from guinea‐pig hearts by combining the techniques of whole‐cell voltage clamp and intracellular perfusion and showed almost exponential voltage dependence.

Measurement of reversal potential of Na+‐Ca2+ exchange current in single guinea‐pig ventricular cells.

The result indicates that [Ca2+]i, at least under the cell membrane, changes due to ion fluxes through the Na+‐ Ca2+ exchange and that control of the ion concentrations within the cell is prerequisite for measuring the reversal potential of the Na-Ca2- exchange.

Effect of membrane potential changes on the calcium transient in single rat cardiac muscle cells.

Using the calcium indicator fura-2 under voltage-clamp conditions, changes in intracellular calcium could be monitored in single rat ventricular cells while controlling membrane potential, suggesting that only a small fraction of Isi is required to trigger calcium release from the sarcoplasmic reticulum.

Ion transport by the Na-Ca exchange in isolated rod outer segments.

It is proposed that the voltage dependence of the exchange is due to the external Na+-binding site being sensitive to membrane potential, perhaps because it is located within the membrane electric field.

Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development

Under the conditions the authors have studied, delta muNa and delta muCa appeared to be coupled and n was nearly constant at 2.5, as would be expected if the Na-Ca exchange system was able to set the steady level of alpha iCa.