© 1997 American Heart Association, Inc.
Articles |
Low Efficiency of Ca2+ Entry Through the Na+-Ca2+ Exchanger as Trigger for Ca2+ Release From the Sarcoplasmic Reticulum
A Comparison Between L-Type Ca2+ Current and Reverse-Mode Na+-Ca2+ Exchange
From the Laboratory of Experimental Cardiology (K.R.S., F. Van de W.), University of Leuven (Belgium), and the Laboratory of Electrobiology (M.M.), University of Antwerp (Belgium).
Correspondence to Karin R. Sipido, MD, PhD, Laboratory of Experimental Cardiology, K.U.L., Campus Gasthuisberg O/N 7th Floor, Herestraat 49, B-3000 Leuven, Belgium. E-mail Karin.Sipido{at}med.kuleuven.ac.be.
Abstract It has been proposed that Ca2+ entry through the Na+-Ca2+ exchanger can contribute significantly to the trigger for Ca2+ release from the sarcoplasmic reticulum (SR). We have compared the characteristics of Ca2+ release triggered by reverse-mode Na+-Ca2+ exchange and by L-type Ca2+ current (ICaL) during depolarizing steps in single guinea pig ventricular myocytes (whole-cell voltage clamp, fluo 3 and fura-red as [Ca2+]i indicators, 36±1°C, K+-based pipette solution with 20 mmol/L [Na+]). Conditioning pulses to +60 mV ensured comparable Ca2+ loading of the SR. In the presence of ICaL, [Ca2+]i transients typically have an early and rapid rising phase reflecting Ca2+ release, which has a bell-shaped voltage dependence with a peak at +10 mV. With Ca2+ entry through Na+-Ca2+ exchange only (20 µmol/L nisoldipine), Ca2+ release flux from the SR is decreased and directly related to the amplitude of the depolarizing step. Ca2+ release is preceded by a significant delay (81±21 ms at +20 mV, 24±4 ms at +70 mV) related to Ca2+ entry through the exchanger. Triggered release interrupts Ca2+ entry, as evidenced by reversal of the exchanger current. At potentials positive to +40 mV, Ca2+ influx through Na+-Ca2+ exchange, calculated from the outward exchange current, reaches magnitudes comparable to ICaL, but Ca2+ release due to reverse-mode Na+-Ca2+ exchange still has a significant delay. We calculated trigger efficiency as the ratio between the maximal rate of Ca2+ release and the Ca2+ influx preceding this release; efficiency of reverse-mode Na+-Ca2+ exchange is approximately four times less than that of ICaL. With both ICaL and reverse-mode Na+-Ca2+ exchange present, Ca2+ release is triggered by ICaL, and a contribution of reverse-mode Na+-Ca2+ exchange to the trigger could not be detected at potentials below +60 mV. These characteristics of reverse-mode Na+-Ca2+ exchange predict that its role as a trigger for Ca2+ release during the action potential is likely to be negligible.
Key Words: Na+-Ca2+ exchange • sarcoplasmic reticulum • Ca2+ channel • cardiomyocyte
This article has been cited by other articles:
 |
|
 |
|
  E. A. Sobie, M. B. Cannell, and J. H. B. Bridge Allosteric Activation of Na+-Ca2+ Exchange by L-Type Ca2+ Current Augments the Trigger Flux for SR Ca2+ Release in Ventricular Myocytes Biophys. J., April 1, 2008; 94(7): L54 - L56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, L. Hove-Madsen, and G. F. Tibbits Ontogeny of Ca2+-induced Ca2+ release in rabbit ventricular myocytes Am J Physiol Cell Physiol, February 1, 2008; 294(2): C516 - C525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Orchard and F. Brette t-tubules and sarcoplasmic reticulum function in cardiac ventricular myocytes Cardiovasc Res, January 15, 2008; 77(2): 237 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Dan, E. Lin, J. Huang, P. Biln, and G. F. Tibbits Three-Dimensional Distribution of Cardiac Na+-Ca2+ Exchanger and Ryanodine Receptor during Development Biophys. J., October 1, 2007; 93(7): 2504 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Altamirano and D. M. Bers Voltage Dependence of Cardiac Excitation Contraction Coupling: Unitary Ca2+ Current Amplitude and Open Channel Probability Circ. Res., September 14, 2007; 101(6): 590 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schotten, S. de Haan, S. Verheule, E. G.A. Harks, D. Frechen, E. Bodewig, M. Greiser, R. Ram, J. Maessen, M. Kelm, et al. Blockade of atrial-specific K+-currents increases atrial but not ventricular contractility by enhancing reverse mode Na+/Ca2+-exchange Cardiovasc Res, January 1, 2007; 73(1): 37 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Lines, J. B. Sande, W. E. Louch, H. K. Mork, P. Grottum, and O. M. Sejersted Contribution of the Na+/Ca2+ Exchanger to Rapid Ca2+ Release in Cardiomyocytes Biophys. J., August 1, 2006; 91(3): 779 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, L. Xu, M. Thomas, K. Whitaker, L. Hove-Madsen, and G. F. Tibbits L-type Ca2+ channel function and expression in neonatal rabbit ventricular myocytes Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2267 - H2276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brette and C. H. Orchard No Apparent Requirement for Neuronal Sodium Channels in Excitation-Contraction Coupling in Rat Ventricular Myocytes Circ. Res., March 17, 2006; 98(5): 667 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bito, D. Dauwe, F. Verdonck, K. Mubagwa, and K. R. Sipido The Amiodarone Derivative KB130015 [2-Methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran] Induces an Na+-Dependent Increase of [Ca2+] in Ventricular Myocytes J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 162 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brette, L. Salle, and C. H. Orchard Quantification of Calcium Entry at the T-Tubules and Surface Membrane in Rat Ventricular Myocytes Biophys. J., January 1, 2006; 90(1): 381 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Inoue and J. H. B. Bridge Variability in Couplon Size in Rabbit Ventricular Myocytes Biophys. J., November 1, 2005; 89(5): 3102 - 3110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Reuter, C. Pott, J. I. Goldhaber, S. A. Henderson, K. D. Philipson, and R. H.G. Schwinger Na+-Ca2+exchange in the regulation of cardiac excitation-contraction coupling Cardiovasc Res, August 1, 2005; 67(2): 198 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Eisner and K. R. Sipido Sodium Calcium Exchange in the Heart: Necessity or Luxury? Circ. Res., September 17, 2004; 95(6): 549 - 551. [Full Text] [PDF]
|
|
|
|
|
|
M. R Fowler, R. S Dobson, C. H Orchard, and S. M Harrison Functional consequences of detubulation of isolated rat ventricular myocytes Cardiovasc Res, June 1, 2004; 62(3): 529 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chorvatova, G. Hart, and M. Hussain Na+/Ca2+ exchange current (INa/Ca) and sarcoplasmic reticulum Ca2+ release in catecholamine-induced cardiac hypertrophy Cardiovasc Res, February 1, 2004; 61(2): 278 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Armoundas, I. A. Hobai, G. F. Tomaselli, R. L. Winslow, and B. O'Rourke Role of Sodium-Calcium Exchanger in Modulating the Action Potential of Ventricular Myocytes From Normal and Failing Hearts Circ. Res., July 11, 2003; 93(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brette and C. Orchard T-Tubule Function in Mammalian Cardiac Myocytes Circ. Res., June 13, 2003; 92(11): 1182 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Mummery, D. Ward-van Oostwaard, P. Doevendans, R. Spijker, S. van den Brink, R. Hassink, M. van der Heyden, T. Opthof, M. Pera, A. B. de la Riviere, et al. Differentiation of Human Embryonic Stem Cells to Cardiomyocytes: Role of Coculture With Visceral Endoderm-Like Cells Circulation, June 3, 2003; 107(21): 2733 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Weber, K. S. Ginsburg, and D. M. Bers Cardiac Submembrane [Na+] Transients Sensed by Na+-Ca2+ Exchange Current Circ. Res., May 16, 2003; 92(9): 950 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Antoons, M. Ver Heyen, L. Raeymaekers, P. Vangheluwe, F. Wuytack, and K. R. Sipido Ca2+ Uptake by the Sarcoplasmic Reticulum in Ventricular Myocytes of the SERCA2b/b Mouse Is Impaired at Higher Ca2+ Loads Only Circ. Res., May 2, 2003; 92(8): 881 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hove-Madsen, A. Llach, G. F. Tibbits, and L. Tort Triggering of sarcoplasmic reticulum Ca2+ release and contraction by reverse mode Na+/Ca2+ exchange in trout atrial myocytes Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1330 - R1339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Balke and L. Goldman Excitation Contraction Coupling in Cardiac Muscle: Is there a Purely Voltage-dependent Component? J. Gen. Physiol., April 28, 2003; 121(5): 349 - 352. [Full Text] [PDF]
|
|
|
|
|
|
M. Inoue and J. H.B. Bridge Ca2+ Sparks in Rabbit Ventricular Myocytes Evoked by Action Potentials: Involvement of Clusters of L-Type Ca2+ Channels Circ. Res., March 21, 2003; 92(5): 532 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pieske and S. R Houser [Na+]i handling in the failing human heart Cardiovasc Res, March 15, 2003; 57(4): 874 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Schillinger, J. W Fiolet, K. Schlotthauer, and G. Hasenfuss Relevance of Na+-Ca2+ exchange in heart failure Cardiovasc Res, March 15, 2003; 57(4): 921 - 933. [Full Text] [PDF]
|
|
|
|
|
|
A Baartscheer, C.A Schumacher, C.N.W Belterman, R Coronel, and J.W.T Fiolet [Na+]i and the driving force of the Na+/Ca2+-exchanger in heart failure Cardiovasc Res, March 15, 2003; 57(4): 986 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kurata, I. Hisatome, S. Imanishi, and T. Shibamoto Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2074 - H2101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Piacentino III, J. P. Gaughan, and S. R. Houser L-Type Ca2+ Currents Overlapping Threshold Na+ Currents: Could They Be Responsible for the "Slip-Mode" Phenomenon in Cardiac Myocytes? Circ. Res., March 8, 2002; 90(4): 435 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R Sipido, P. G.A Volders, M. A Vos, and F. Verdonck Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc Res, March 1, 2002; 53(4): 782 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Weber, V. Piacentino III, K. S. Ginsburg, S. R. Houser, and D. M. Bers Na+-Ca2+ Exchange Current and Submembrane [Ca2+] During the Cardiac Action Potential Circ. Res., February 8, 2002; 90(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Sharma and L. Tung Effects of uniform electric fields on intracellular calcium transients in single cardiac cells Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H72 - H79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. An, S. G. Varadarajan, A. Camara, Q. Chen, E. Novalija, G. J. Gross, and D. F. Stowe Blocking Na+/H+ exchange reduces [Na+]i and [Ca2+]i load after ischemia and improves function in intact hearts Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2398 - H2409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shigekawa and T. Iwamoto Cardiac Na+-Ca2+ Exchange : Molecular and Pharmacological Aspects Circ. Res., May 11, 2001; 88(9): 864 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Ferrier and S. E. Howlett Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H1928 - H1944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido, P. G. A. Volders, S. H. M. de Groot, F. Verdonck, F. Van de Werf, H. J. J. Wellens, and M. A. Vos Enhanced Ca2+ Release and Na/Ca Exchange Activity in Hypertrophied Canine Ventricular Myocytes : Potential Link Between Contractile Adaptation and Arrhythmogenesis Circulation, October 24, 2000; 102(17): 2137 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Barry Na+-Ca2+ Exchange in Failing Myocardium : Friend or Foe? Circ. Res., September 29, 2000; 87(7): 529 - 531. [Full Text] [PDF]
|
|
|
|
|
|
W. Schillinger, P. M. L. Janssen, S. Emami, S. A. Henderson, R. S. Ross, N. Teucher, O. Zeitz, K. D. Philipson, J. Prestle, and G. Hasenfuss Impaired Contractile Performance of Cultured Rabbit Ventricular Myocytes After Adenoviral Gene Transfer of Na+-Ca2+ Exchanger Circ. Res., September 29, 2000; 87(7): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Bers Calcium Fluxes Involved in Control of Cardiac Myocyte Contraction Circ. Res., August 18, 2000; 87(4): 275 - 281. [Full Text] [PDF]
|
|
|
|
|
|
J.-B. Shen, B. Jiang, and A. J. Pappano Comparison of L-Type Calcium Channel Blockade by Nifedipine and/or Cadmium in Guinea Pig Ventricular Myocytes J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 562 - 570. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Pan, T. Iwamoto, A. Uehara, T. Y. Nakamura, I. Imanaga, and M. Shigekawa Physiological functions of the regulatory domains of the cardiac Na+/Ca2+ exchanger NCX1 Am J Physiol Cell Physiol, August 1, 2000; 279(2): C393 - C402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wasserstrom, E. Holt, I. Sjaastad, P. K. Lunde, A. Odegaard, and O. M. Sejersted Altered E-C coupling in rat ventricular myocytes from failing hearts 6 wk after MI Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H798 - H807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G.A. Volders, M. A. Vos, B. Szabo, K. R. Sipido, S.H.M. de Groot, A. P.M. Gorgels, H. J.J. Wellens, and R. Lazzara Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts Cardiovasc Res, June 1, 2000; 46(3): 376 - 392. [Full Text] [PDF]
|
|
|
|
|
|
H. Satoh, K. S. Ginsburg, K. Qing, H. Terada, H. Hayashi, and D. M. Bers KB-R7943 Block of Ca2+ Influx Via Na+/Ca2+ Exchange Does Not Alter Twitches or Glycoside Inotropy but Prevents Ca2+ Overload in Rat Ventricular Myocytes Circulation, March 28, 2000; 101(12): 1441 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Stankovicova, M. Szilard, I De Scheerder, and K. R Sipido M cells and transmural heterogeneity of action potential configuration in myocytes from the left ventricular wall of the pig heart Cardiovasc Res, March 1, 2000; 45(4): 952 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.W.T Fiolet and A Baartscheer Cellular calcium homeostasis during ischemia; a thermodynamic approach Cardiovasc Res, January 1, 2000; 45(1): 100 - 106. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wasserstrom and A.-M. Vites Activation of contraction in cat ventricular myocytes: effects of low Cd2+ concentration and temperature Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H488 - H498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M Bers and E. Perez-Reyes Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release Cardiovasc Res, May 1, 1999; 42(2): 339 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Cross, L. Lu, C. Steenbergen, K. D. Philipson, and E. Murphy Overexpression of the Cardiac Na+/Ca2+ Exchanger Increases Susceptibility to Ischemia/Reperfusion Injury in Male, but Not Female, Transgenic Mice Circ. Res., December 14, 1998; 83(12): 1215 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. A. Volders, K. R. Sipido, M. A. Vos, A. Kulcsar, S. C. Verduyn, and H. J. J. Wellens Cellular Basis of Biventricular Hypertrophy and Arrhythmogenesis in Dogs With Chronic Complete Atrioventricular Block and Acquired Torsade de Pointes Circulation, September 15, 1998; 98(11): 1136 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.A Eisner, A.W Trafford, M.E Dnaz, C.L Overend, and S.C O'Neill The control of Ca release from the cardiac sarcoplasmic reticulum: regulation versus autoregulation Cardiovasc Res, June 1, 1998; 38(3): 589 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Weber, V. Piacentino III, K. S. Ginsburg, S. R. Houser, and D. M. Bers Na+-Ca2+ Exchange Current and Submembrane [Ca2+] During the Cardiac Action Potential Circ. Res., February 8, 2002; 90(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Piacentino III, J. P. Gaughan, and S. R. Houser L-Type Ca2+ Currents Overlapping Threshold Na+ Currents: Could They Be Responsible for the "Slip-Mode" Phenomenon in Cardiac Myocytes? Circ. Res., March 8, 2002; 90(4): 435 - 442. [Abstract] [Full Text] [PDF]
|
|