Circulation Research. 2002
Published online before print August 29, 2002, doi: 10.1161/01.RES.0000035527.53514.C2
Published online before print August 29, 2002, doi: 10.1161/01.RES.0000035527.53514.C2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 12, 2002
Revised on August 16, 2002
Accepted on August 19, 2002
Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca2+ Transient in Rat Ventricular Myocytes
M. E. Díaz ;
From the Unit of Cardiac Physiology, University of Manchester, Manchester, UK.
* To whom correspondence should be addressed. E-mail: eisner{at}man.ac.uk.
Sarcoplasmic reticulum (SR) Ca2+ release, through the ryanodine receptor (RyR), is essential for the systolic Ca2+ transient and thus the cardiac contractile function. The aim of this study was to examine the effects on the spatial organization of the systolic Ca2+ transient of depressing RyR open probability (Po) with tetracaine or intracellular acidification. Voltage-clamped, fluo-3-loaded myocytes were studied using confocal microscopy. Depressing RyR Po increased the variability of the Ca2+ transient amplitude between different regions of the cell. This variability often produced alternans with a region producing large and small transients alternately. In addition, the raising phase of the Ca2+ transient became biphasic. The initial phase was constant but the second was variable and propagated as a wave through part of the cell. That both phases involved SR Ca2+ release was shown by their reduction by caffeine. Regional [Ca2+]i alternans was accompanied by a much smaller degree of alternans at the whole cell level. We suggest that, in tetracaine or acidosis, the initial phase of the Ca2+ transient results from Ca2+ release via RyRs directly activated by adjacent L-type Ca2+ channels. At some sites, this will activate neighboring RyRs and a Ca2+ wave will propagate via activation of other RyRs. This work is the first demonstration that decreased RyR Po alone can produce disarray of the Ca2+ release process and initiate alternans.
Key words: calcium • ryanodine receptor • alternans
This article has been cited by other articles:
 |
|
 |
|
  L.-H. Xie and J. N. Weiss Arrhythmogenic consequences of intracellular calcium waves Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H997 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Gaeta, G. Bub, G. W. Abbott, and D. J. Christini Dynamical Mechanism for Subcellular Alternans in Cardiac Myocytes Circ. Res., August 14, 2009; 105(4): 335 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Koivumaki, J. Takalo, T. Korhonen, P. Tavi, and M. Weckstrom Modelling sarcoplasmic reticulum calcium ATPase and its regulation in cardiac myocytes Phil Trans R Soc A, June 13, 2009; 367(1896): 2181 - 2202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Wasserstrom, R. Sharma, S. Kapur, J. E. Kelly, A. H. Kadish, C. W. Balke, and G. L. Aistrup Multiple Defects in Intracellular Calcium Cycling in Whole Failing Rat Heart Circ Heart Fail, May 1, 2009; 2(3): 223 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kapur, J. A. Wasserstrom, J. E. Kelly, A. H. Kadish, and G. L. Aistrup Acidosis and ischemia increase cellular Ca2+ transient alternans and repolarization alternans susceptibility in the intact rat heart Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1491 - H1512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, M. E. Diaz, D. A. Eisner, and S. O'Neill The effects of membrane potential, SR Ca2+ content and RyR responsiveness on systolic Ca2+ alternans in rat ventricular myocytes J. Physiol., March 15, 2009; 587(6): 1283 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Aistrup, Y. Shiferaw, S. Kapur, A. H. Kadish, and J. A. Wasserstrom Mechanisms Underlying the Formation and Dynamics of Subcellular Calcium Alternans in the Intact Rat Heart Circ. Res., March 13, 2009; 104(5): 639 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tao, S. C. O'Neill, M. E. Diaz, Y. T. Li, D. A. Eisner, and H. Zhang Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H598 - H609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Heinzel, V. Bito, L. Biesmans, M. Wu, E. Detre, F. von Wegner, P. Claus, S. Dymarkowski, F. Maes, J. Bogaert, et al. Remodeling of T-Tubules and Reduced Synchrony of Ca2+ Release in Myocytes From Chronically Ischemic Myocardium Circ. Res., February 15, 2008; 102(3): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. de Diego, F. Chen, L.-H. Xie, A. S. Dave, M. Thu, C. Rongey, J. N. Weiss, and M. Valderrabano Cardiac alternans in embryonic mouse ventricles Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H433 - H440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Jiang, W. Chen, R. Wang, L. Zhang, and S. R. W. Chen Loss of luminal Ca2+ activation in the cardiac ryanodine receptor is associated with ventricular fibrillation and sudden death PNAS, November 13, 2007; 104(46): 18309 - 18314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qu and J. N. Weiss The chicken or the egg? Voltage and calcium dynamics in the heart Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2054 - H2055. [Full Text] [PDF]
|
|
|
|
|
|
V. E. Bondarenko and R. L. Rasmusson Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1816 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Bootman, D. R. Higazi, S. Coombes, and H. L. Roderick Calcium signalling during excitation-contraction coupling in mammalian atrial myocytes. J. Cell Sci., October 1, 2006; 119(Pt 19): 3915 - 3925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Picht, J. DeSantiago, L. A. Blatter, and D. M. Bers Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations Circ. Res., September 29, 2006; 99(7): 740 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Aistrup, J. E. Kelly, S. Kapur, M. Kowalczyk, I. Sysman-Wolpin, A. H. Kadish, and J. A. Wasserstrom Pacing-induced Heterogeneities in Intracellular Ca2+ Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart Circ. Res., September 29, 2006; 99(7): E65 - E73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sato, Y. Shiferaw, A. Garfinkel, J. N. Weiss, Z. Qu, and A. Karma Spatially Discordant Alternans in Cardiac Tissue: Role of Calcium Cycling Circ. Res., September 1, 2006; 99(5): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Weiss, A. Karma, Y. Shiferaw, P.-S. Chen, A. Garfinkel, and Z. Qu From Pulsus to Pulseless: The Saga of Cardiac Alternans Circ. Res., May 26, 2006; 98(10): 1244 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.A. Venetucci, A.W. Trafford, M.E. Diaz, S.C. O'Neill, and D.A. Eisner Reducing Ryanodine Receptor Open Probability as a Means to Abolish Spontaneous Ca2+ Release and Increase Ca2+ Transient Amplitude in Adult Ventricular Myocytes Circ. Res., May 26, 2006; 98(10): 1299 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Iribe, P. Kohl, and D. Noble Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2+ handling and interval-force relations: a modelling study Phil Trans R Soc A, May 15, 2006; 364(1842): 1107 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shiferaw and A. Karma Turing instability mediated by voltage and calcium diffusion in paced cardiac cells PNAS, April 11, 2006; 103(15): 5670 - 5675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-S. Song, E. A. Sobie, S. McCulle, W. J. Lederer, C. W. Balke, and H. Cheng Orphaned ryanodine receptors in the failing heart. PNAS, March 14, 2006; 103(11): 4305 - 4310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Litwin "Ryanogate": Who Leaked the Calcium? Circ. Res., February 3, 2006; 98(2): 165 - 168. [Full Text] [PDF]
|
|
|
|
|
|
J. Kockskamper, A. V. Zima, and L. A. Blatter Modulation of sarcoplasmic reticulum Ca2+ release by glycolysis in cat atrial myocytes J. Physiol., May 1, 2005; 564(3): 697 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Goldhaber, L.-H. Xie, T. Duong, C. Motter, K. Khuu, and J. N. Weiss Action Potential Duration Restitution and Alternans in Rabbit Ventricular Myocytes: The Key Role of Intracellular Calcium Cycling Circ. Res., March 4, 2005; 96(4): 459 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Eisner, M. E. Diaz, Y. Li, S. C. O'Neill, and A. W. Trafford Stability and instability of regulation of intracellular calcium Exp Physiol, January 1, 2005; 90(1): 3 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lakireddy, P. Baweja, A. Syed, G. Bub, M. Boutjdir, and N. El-Sherif Contrasting effects of ischemia on the kinetics of membrane voltage and intracellular calcium transient underlie electrical alternans Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H400 - H407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Lowri Thomas, C. H. George, and F. Anthony Lai Functional heterogeneity of ryanodine receptor mutations associated with sudden cardiac death Cardiovasc Res, October 1, 2004; 64(1): 52 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. O'Neill, L. Miller, R. Hinch, and D. A. Eisner Interplay between SERCA and sarcolemmal Ca2+ efflux pathways controls spontaneous release of Ca2+ from the sarcoplasmic reticulum in rat ventricular myocytes J. Physiol., August 15, 2004; 559(1): 121 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido Understanding Cardiac Alternans: The Answer Lies in the Ca2+ Store Circ. Res., March 19, 2004; 94(5): 570 - 572. [Full Text] [PDF]
|
|
|
|
|
|
M. E. Diaz, S. C. O'Neill, and D. A. Eisner Sarcoplasmic Reticulum Calcium Content Fluctuation Is the Key to Cardiac Alternans Circ. Res., March 19, 2004; 94(5): 650 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Sanguinetti and P. B. Bennett Antiarrhythmic Drug Target Choices and Screening Circ. Res., September 19, 2003; 93(6): 491 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Seidler, S. L.W. Miller, C. M. Loughrey, A. Kania, A. Burow, S. Kettlewell, N. Teucher, S. Wagner, H. Kogler, M. B. Meyers, et al. Effects of Adenovirus-Mediated Sorcin Overexpression on Excitation-Contraction Coupling in Isolated Rabbit Cardiomyocytes Circ. Res., July 25, 2003; 93(2): 132 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Verrier, A. V. Tolat, and M. E. Josephson T-Wave alternans for arrhythmia risk stratification in patients with idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2225 - 2227. [Full Text] [PDF]
|
|
|
|
|
|
K. R. Laurita, R. Katra, B. Wible, X. Wan, and M. H. Koo Transmural Heterogeneity of Calcium Handling in Canine Circ. Res., April 4, 2003; 92(6): 668 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.A. Eisner and A.W. Trafford Heart Failure and the Ryanodine Receptor: Does Occam's Razor Rule? Circ. Res., November 29, 2002; 91(11): 979 - 981. [Full Text] [PDF]
|
|
|
|
|
|
J. Kockskamper and L. A Blatter Subcellular Ca2+ alternans represents a novel mechanism for the generation of arrhythmogenic Ca2+ waves in cat atrial myocytes J. Physiol., November 15, 2002; 545(1): 65 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pieske and J. Kockskamper Alternans Goes Subcellular: A "Disease" of the Ryanodine Receptor? Circ. Res., October 4, 2002; 91(7): 553 - 555. [Full Text] [PDF]
|
|