Published online before print November 7, 2002, doi: 10.1161/01.RES.0000045940.67060.DD
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 28, 2002
Revised on October 28, 2002
Accepted on October 28, 2002
Spatial and Temporal Inhomogeneities During Ca2+ Release From the Sarcoplasmic Reticulum in Pig Ventricular Myocytes
Frank R. Heinzel ;
From the Laboratory of Experimental Cardiology (F.R.H., V.B., P.G.A.V., G.A., K.R.S.) and the Center for Experimental Surgery (K.M.), University of Leuven, Leuven, Belgium; the Institute of Pathophysiology (F.R.H.), University of Essen, Essen, Germany; and the Department of Cardiology (P.G.A.V.), Academic Hospital Maastricht, Maastricht, the Netherlands.
* To whom correspondence should be addressed. E-mail: Karin.Sipido{at}med.kuleuven.ac.be.
The [Ca2+]i transient of ventricular myocytes during normal excitation-contraction coupling is the summation of primary Ca2+ release events, which originate at the junction of the sarcoplasmic reticulum (SR) and the T-tubular system. Studies in small mammals have shown a high density of release sites, but little is known of larger mammals. We have studied the spatial distribution of SR Ca2+ release in pig ventricular myocytes using a confocal microscopy. In 69 of 107 cells, large inhomogeneities of Ca2+ release were observed along the longitudinal scan line. Areas where the increase of [Ca2+]i was delayed (time to 50% of peak F/F [where F indicates fluorescence intensity, and F indicates F at rest] was 26±1 ms in delayed areas versus 11±2 ms in early areas) and smaller (peak F/F was 2.27±0.10 for delayed areas versus 2.69±0.13 for early areas; n=13 cells, P<0.05) could be up to 26 µm wide. The sum of all delayed areas could make up to 55% of the line scan. The spatial pattern was constant during steady-state stimulation and was not altered by enhancing Ca2+ channel opening or SR Ca2+ content (Bay K8644, isoproterenol). Imaging of sarcolemmal membranes revealed several areas devoid of T tubules, but SR Ca2+ release channels were homogeneously distributed. In contrast, compared with pig myocytes, mouse myocytes had a very dense T-tubular network, no large inhomogeneities of release, and a faster rate of rise of [Ca2+]i. In conclusion, in pig ventricular myocytes, areas of delayed release are related to regional absence of T tubules but not ryanodine receptors. This lower number of functional couplons contributes to a slower overall rate of rise of [Ca2+]i.
Key words: ventricular myocytes • calcium • sarcoplasmic reticulum • pigs
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 A. R. Lyon, K. T. MacLeod, Y. Zhang, E. Garcia, G. K. Kanda, M. J. Lab, Y. E. Korchev, S. E. Harding, and J. Gorelik Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart PNAS, April 21, 2009; 106(16): 6854 - 6859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Heinzel, P. Gres, K. Boengler, A. Duschin, I. Konietzka, T. Rassaf, J. Snedovskaya, S. Meyer, A. Skyschally, M. Kelm, et al. Inducible Nitric Oxide Synthase Expression and Cardiomyocyte Dysfunction During Sustained Moderate Ischemia in Pigs Circ. Res., November 7, 2008; 103(10): 1120 - 1127. [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. 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]
|
|
|
|
|
|
M. Warren, J. F. Huizar, A. G. Shvedko, and A. V. Zaitsev Spatiotemporal Relationship Between Intracellular Ca2+ Dynamics and Wave Fragmentation During Ventricular Fibrillation in Isolated Blood-Perfused Pig Hearts Circ. Res., October 26, 2007; 101(9): e90 - e101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido and S. P. Janssens How Old Is Your Heart? Circ. Res., August 17, 2007; 101(4): 323 - 325. [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Louch, H. K. Mork, J. Sexton, T. A. Stromme, P. Laake, I. Sjaastad, and O. M. Sejersted T-tubule disorganization and reduced synchrony of Ca2+ release in murine cardiomyocytes following myocardial infarction J. Physiol., July 15, 2006; 574(2): 519 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Heinzel, Y. Luo, G. Dodoni, K. Boengler, F. Petrat, F. Di Lisa, H. de Groot, R. Schulz, and G. Heusch Formation of reactive oxygen species at increased contraction frequency in rat cardiomyocytes Cardiovasc Res, July 15, 2006; 71(2): 374 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Litwin "Ryanogate": Who Leaked the Calcium? Circ. Res., February 3, 2006; 98(2): 165 - 168. [Full Text] [PDF]
|
|
|
|
 |
|
 P. P. Sengupta, B. K. Khandheria, J. Korinek, J. Wang, A. Jahangir, J. B. Seward, and M. Belohlavek Apex-to-Base Dispersion in Regional Timing of Left Ventricular Shortening and Lengthening J. Am. Coll. Cardiol., January 3, 2006; 47(1): 163 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-S. Song, Y. Pi, S.-J. Kim, A. Yatani, S. Guatimosim, R. K. Kudej, Q. Zhang, H. Cheng, L. Hittinger, B. Ghaleh, et al. Paradoxical Cellular Ca2+ Signaling in Severe but Compensated Canine Left Ventricular Hypertrophy Circ. Res., September 2, 2005; 97(5): 457 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Boengler, G. Dodoni, A. Rodriguez-Sinovas, A. Cabestrero, M. Ruiz-Meana, P. Gres, I. Konietzka, C. Lopez-Iglesias, D. Garcia-Dorado, F. Di Lisa, et al. Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning Cardiovasc Res, August 1, 2005; 67(2): 234 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Shiels and E. White Temporal and spatial properties of cellular Ca2+ flux in trout ventricular myocytes Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1756 - R1766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Fowler, J. R. Naz, M. D. Graham, G. Bru-Mercier, S. M. Harrison, and C. H. Orchard Decreased Ca2+ extrusion via Na+/Ca2+ exchange in epicardial left ventricular myocytes during compensated hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2431 - H2438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rubart Two-Photon Microscopy of Cells and Tissue Circ. Res., December 10, 2004; 95(12): 1154 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Cordeiro, L. Greene, C. Heilmann, D. Antzelevitch, and C. Antzelevitch Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1471 - H1479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E Louch, V. Bito, F. R Heinzel, R. Macianskiene, J. Vanhaecke, W. Flameng, K. Mubagwa, and K. R Sipido Reduced synchrony of Ca2+ release with loss of T-tubules--a comparison to Ca2+ release in human failing cardiomyocytes Cardiovasc Res, April 1, 2004; 62(1): 63 - 73. [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]
|
|