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. 2002 Dec;83(6):2918–2945. doi: 10.1016/S0006-3495(02)75301-0

An integrative model of the cardiac ventricular myocyte incorporating local control of Ca2+ release.

Joseph L Greenstein 1, Raimond L Winslow 1
PMCID: PMC1201479  PMID: 12496068

Abstract

The local control theory of excitation-contraction (EC) coupling in cardiac muscle asserts that L-type Ca(2+) current tightly controls Ca(2+) release from the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type Ca(2+) channels (LCCs) and ryanodine receptors (RyRs). These local interactions give rise to smoothly graded Ca(2+)-induced Ca(2+) release (CICR), which exhibits high gain. In this study we present a biophysically detailed model of the normal canine ventricular myocyte that conforms to local control theory. The model formulation incorporates details of microscopic EC coupling properties in the form of Ca(2+) release units (CaRUs) in which individual sarcolemmal LCCs interact in a stochastic manner with nearby RyRs in localized regions where junctional SR membrane and transverse-tubular membrane are in close proximity. The CaRUs are embedded within and interact with the global systems of the myocyte describing ionic and membrane pump/exchanger currents, SR Ca(2+) uptake, and time-varying cytosolic ion concentrations to form a model of the cardiac action potential (AP). The model can reproduce both the detailed properties of EC coupling, such as variable gain and graded SR Ca(2+) release, and whole-cell phenomena, such as modulation of AP duration by SR Ca(2+) release. Simulations indicate that the local control paradigm predicts stable APs when the L-type Ca(2+) current is adjusted in accord with the balance between voltage- and Ca(2+)-dependent inactivation processes as measured experimentally, a scenario where common pool models become unstable. The local control myocyte model provides a means for studying the interrelationship between microscopic and macroscopic behaviors in a manner that would not be possible in experiments.

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Selected References

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  1. Ahmmed G. U., Dong P. H., Song G., Ball N. A., Xu Y., Walsh R. A., Chiamvimonvat N. Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure. Circ Res. 2000 Mar 17;86(5):558–570. doi: 10.1161/01.res.86.5.558. [DOI] [PubMed] [Google Scholar]
  2. Arkin A., Ross J., McAdams H. H. Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells. Genetics. 1998 Aug;149(4):1633–1648. doi: 10.1093/genetics/149.4.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bassani J. W., Yuan W., Bers D. M. Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes. Am J Physiol. 1995 May;268(5 Pt 1):C1313–C1319. doi: 10.1152/ajpcell.1995.268.5.C1313. [DOI] [PubMed] [Google Scholar]
  4. Bers D. M., Perez-Reyes E. Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release. Cardiovasc Res. 1999 May;42(2):339–360. doi: 10.1016/s0008-6363(99)00038-3. [DOI] [PubMed] [Google Scholar]
  5. Beuckelmann D. J., Wier W. G. Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J Physiol. 1988 Nov;405:233–255. doi: 10.1113/jphysiol.1988.sp017331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cannell M. B., Berlin J. R., Lederer W. J. Effect of membrane potential changes on the calcium transient in single rat cardiac muscle cells. Science. 1987 Dec 4;238(4832):1419–1423. doi: 10.1126/science.2446391. [DOI] [PubMed] [Google Scholar]
  7. Cannell M. B., Cheng H., Lederer W. J. Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes. Biophys J. 1994 Nov;67(5):1942–1956. doi: 10.1016/S0006-3495(94)80677-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cannell M. B., Cheng H., Lederer W. J. The control of calcium release in heart muscle. Science. 1995 May 19;268(5213):1045–1049. doi: 10.1126/science.7754384. [DOI] [PubMed] [Google Scholar]
  9. Cannell M. B., Soeller C. Numerical analysis of ryanodine receptor activation by L-type channel activity in the cardiac muscle diad. Biophys J. 1997 Jul;73(1):112–122. doi: 10.1016/S0006-3495(97)78052-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cheng H., Fill M., Valdivia H., Lederer W. J. Models of Ca2+ release channel adaptation. Science. 1995 Mar 31;267(5206):2009–2010. doi: 10.1126/science.7701326. [DOI] [PubMed] [Google Scholar]
  11. Cheng H., Lederer W. J., Cannell M. B. Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science. 1993 Oct 29;262(5134):740–744. doi: 10.1126/science.8235594. [DOI] [PubMed] [Google Scholar]
  12. Cleemann L., Morad M. Role of Ca2+ channel in cardiac excitation-contraction coupling in the rat: evidence from Ca2+ transients and contraction. J Physiol. 1991 Jan;432:283–312. doi: 10.1113/jphysiol.1991.sp018385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Collier M. L., Levesque P. C., Kenyon J. L., Hume J. R. Unitary Cl- channels activated by cytoplasmic Ca2+ in canine ventricular myocytes. Circ Res. 1996 May;78(5):936–944. doi: 10.1161/01.res.78.5.936. [DOI] [PubMed] [Google Scholar]
  14. Collier M. L., Thomas A. P., Berlin J. R. Relationship between L-type Ca2+ current and unitary sarcoplasmic reticulum Ca2+ release events in rat ventricular myocytes. J Physiol. 1999 Apr 1;516(Pt 1):117–128. doi: 10.1111/j.1469-7793.1999.117aa.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davare M. A., Avdonin V., Hall D. D., Peden E. M., Burette A., Weinberg R. J., Horne M. C., Hoshi T., Hell J. W. A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2. Science. 2001 Jul 6;293(5527):98–101. doi: 10.1126/science.293.5527.98. [DOI] [PubMed] [Google Scholar]
  16. Delbridge L. M., Bassani J. W., Bers D. M. Steady-state twitch Ca2+ fluxes and cytosolic Ca2+ buffering in rabbit ventricular myocytes. Am J Physiol. 1996 Jan;270(1 Pt 1):C192–C199. doi: 10.1152/ajpcell.1996.270.1.C192. [DOI] [PubMed] [Google Scholar]
  17. Faber G. M., Rudy Y. Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study. Biophys J. 2000 May;78(5):2392–2404. doi: 10.1016/S0006-3495(00)76783-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fabiato A. Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985 Feb;85(2):247–289. doi: 10.1085/jgp.85.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fox Jeffrey J., McHarg Jennifer L., Gilmour Robert F., Jr Ionic mechanism of electrical alternans. Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H516–H530. doi: 10.1152/ajpheart.00612.2001. [DOI] [PubMed] [Google Scholar]
  20. Franzini-Armstrong C., Protasi F., Ramesh V. Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J. 1999 Sep;77(3):1528–1539. doi: 10.1016/S0006-3495(99)77000-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Greenstein J. L., Wu R., Po S., Tomaselli G. F., Winslow R. L. Role of the calcium-independent transient outward current I(to1) in shaping action potential morphology and duration. Circ Res. 2000 Nov 24;87(11):1026–1033. doi: 10.1161/01.res.87.11.1026. [DOI] [PubMed] [Google Scholar]
  22. Györke S., Fill M. Ryanodine receptor adaptation: control mechanism of Ca(2+)-induced Ca2+ release in heart. Science. 1993 May 7;260(5109):807–809. doi: 10.1126/science.8387229. [DOI] [PubMed] [Google Scholar]
  23. Gómez A. M., Valdivia H. H., Cheng H., Lederer M. R., Santana L. F., Cannell M. B., McCune S. A., Altschuld R. A., Lederer W. J. Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science. 1997 May 2;276(5313):800–806. doi: 10.1126/science.276.5313.800. [DOI] [PubMed] [Google Scholar]
  24. Hadley R. W., Hume J. R. An intrinsic potential-dependent inactivation mechanism associated with calcium channels in guinea-pig myocytes. J Physiol. 1987 Aug;389:205–222. doi: 10.1113/jphysiol.1987.sp016654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Handrock R., Schröder F., Hirt S., Haverich A., Mittmann C., Herzig S. Single-channel properties of L-type calcium channels from failing human ventricle. Cardiovasc Res. 1998 Feb;37(2):445–455. doi: 10.1016/s0008-6363(97)00257-5. [DOI] [PubMed] [Google Scholar]
  26. He J., Conklin M. W., Foell J. D., Wolff M. R., Haworth R. A., Coronado R., Kamp T. J. Reduction in density of transverse tubules and L-type Ca(2+) channels in canine tachycardia-induced heart failure. Cardiovasc Res. 2001 Feb 1;49(2):298–307. doi: 10.1016/s0008-6363(00)00256-x. [DOI] [PubMed] [Google Scholar]
  27. Herzig S., Patil P., Neumann J., Staschen C. M., Yue D. T. Mechanisms of beta-adrenergic stimulation of cardiac Ca2+ channels revealed by discrete-time Markov analysis of slow gating. Biophys J. 1993 Oct;65(4):1599–1612. doi: 10.1016/S0006-3495(93)81199-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hobai I. A., O'Rourke B. Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation-contraction coupling in canine heart failure. Circulation. 2001 Mar 20;103(11):1577–1584. doi: 10.1161/01.cir.103.11.1577. [DOI] [PubMed] [Google Scholar]
  29. Jafri M. S., Rice J. J., Winslow R. L. Cardiac Ca2+ dynamics: the roles of ryanodine receptor adaptation and sarcoplasmic reticulum load. Biophys J. 1998 Mar;74(3):1149–1168. doi: 10.1016/S0006-3495(98)77832-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Janczewski A. M., Spurgeon H. A., Stern M. D., Lakatta E. G. Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells. Am J Physiol. 1995 Feb;268(2 Pt 2):H916–H920. doi: 10.1152/ajpheart.1995.268.2.H916. [DOI] [PubMed] [Google Scholar]
  31. Keizer J., Levine L. Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophys J. 1996 Dec;71(6):3477–3487. doi: 10.1016/S0006-3495(96)79543-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Keizer J., Smith G. D. Spark-to-wave transition: saltatory transmission of calcium waves in cardiac myocytes. Biophys Chem. 1998 May 5;72(1-2):87–100. doi: 10.1016/s0301-4622(98)00125-2. [DOI] [PubMed] [Google Scholar]
  33. Käb S., Nuss H. B., Chiamvimonvat N., O'Rourke B., Pak P. H., Kass D. A., Marban E., Tomaselli G. F. Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure. Circ Res. 1996 Feb;78(2):262–273. doi: 10.1161/01.res.78.2.262. [DOI] [PubMed] [Google Scholar]
  34. Langer G. A., Peskoff A. Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell. Biophys J. 1996 Mar;70(3):1169–1182. doi: 10.1016/S0006-3495(96)79677-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Li G. R., Yang B., Feng J., Bosch R. F., Carrier M., Nattel S. Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes. Am J Physiol. 1999 Jan;276(1 Pt 2):H98–H106. doi: 10.1152/ajpheart.1999.276.1.H98. [DOI] [PubMed] [Google Scholar]
  36. Lindner M., Erdmann E., Beuckelmann D. J. Calcium content of the sarcoplasmic reticulum in isolated ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol. 1998 Apr;30(4):743–749. doi: 10.1006/jmcc.1997.0626. [DOI] [PubMed] [Google Scholar]
  37. Linz K. W., Meyer R. Control of L-type calcium current during the action potential of guinea-pig ventricular myocytes. J Physiol. 1998 Dec 1;513(Pt 2):425–442. doi: 10.1111/j.1469-7793.1998.425bb.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lukyanenko V., Györke I., Györke S. Regulation of calcium release by calcium inside the sarcoplasmic reticulum in ventricular myocytes. Pflugers Arch. 1996 Oct;432(6):1047–1054. doi: 10.1007/s004240050233. [DOI] [PubMed] [Google Scholar]
  39. Luo C. H., Rudy Y. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ Res. 1994 Jun;74(6):1071–1096. doi: 10.1161/01.res.74.6.1071. [DOI] [PubMed] [Google Scholar]
  40. López-López J. R., Shacklock P. S., Balke C. W., Wier W. G. Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science. 1995 May 19;268(5213):1042–1045. doi: 10.1126/science.7754383. [DOI] [PubMed] [Google Scholar]
  41. López-López J. R., Shacklock P. S., Balke C. W., Wier W. G. Local, stochastic release of Ca2+ in voltage-clamped rat heart cells: visualization with confocal microscopy. J Physiol. 1994 Oct 1;480(Pt 1):21–29. doi: 10.1113/jphysiol.1994.sp020337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Marx S. O., Gaburjakova J., Gaburjakova M., Henrikson C., Ondrias K., Marks A. R. Coupled gating between cardiac calcium release channels (ryanodine receptors). Circ Res. 2001 Jun 8;88(11):1151–1158. doi: 10.1161/hh1101.091268. [DOI] [PubMed] [Google Scholar]
  43. Marx S. O., Reiken S., Hisamatsu Y., Jayaraman T., Burkhoff D., Rosemblit N., Marks A. R. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000 May 12;101(4):365–376. doi: 10.1016/s0092-8674(00)80847-8. [DOI] [PubMed] [Google Scholar]
  44. Mazhari R., Greenstein J. L., Winslow R. L., Marbán E., Nuss H. B. Molecular interactions between two long-QT syndrome gene products, HERG and KCNE2, rationalized by in vitro and in silico analysis. Circ Res. 2001 Jul 6;89(1):33–38. doi: 10.1161/hh1301.093633. [DOI] [PubMed] [Google Scholar]
  45. McDonald T. F., Cavalié A., Trautwein W., Pelzer D. Voltage-dependent properties of macroscopic and elementary calcium channel currents in guinea pig ventricular myocytes. Pflugers Arch. 1986 May;406(5):437–448. doi: 10.1007/BF00583365. [DOI] [PubMed] [Google Scholar]
  46. Michailova A., McCulloch A. Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte. Biophys J. 2001 Aug;81(2):614–629. doi: 10.1016/S0006-3495(01)75727-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Noble D., Varghese A., Kohl P., Noble P. Improved guinea-pig ventricular cell model incorporating a diadic space, IKr and IKs, and length- and tension-dependent processes. Can J Cardiol. 1998 Jan;14(1):123–134. [PubMed] [Google Scholar]
  48. Näbauer M., Callewaert G., Cleemann L., Morad M. Regulation of calcium release is gated by calcium current, not gating charge, in cardiac myocytes. Science. 1989 May 19;244(4906):800–803. doi: 10.1126/science.2543067. [DOI] [PubMed] [Google Scholar]
  49. O'Rourke B., Kass D. A., Tomaselli G. F., Käb S., Tunin R., Marbán E. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies. Circ Res. 1999 Mar 19;84(5):562–570. doi: 10.1161/01.res.84.5.562. [DOI] [PubMed] [Google Scholar]
  50. Pandit S. V., Clark R. B., Giles W. R., Demir S. S. A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes. Biophys J. 2001 Dec;81(6):3029–3051. doi: 10.1016/S0006-3495(01)75943-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Parker I., Zang W. J., Wier W. G. Ca2+ sparks involving multiple Ca2+ release sites along Z-lines in rat heart cells. J Physiol. 1996 Nov 15;497(Pt 1):31–38. doi: 10.1113/jphysiol.1996.sp021747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Peterson B. Z., DeMaria C. D., Adelman J. P., Yue D. T. Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels. Neuron. 1999 Mar;22(3):549–558. doi: 10.1016/s0896-6273(00)80709-6. [DOI] [PubMed] [Google Scholar]
  53. Peterson B. Z., Lee J. S., Mulle J. G., Wang Y., de Leon M., Yue D. T. Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels. Biophys J. 2000 Apr;78(4):1906–1920. doi: 10.1016/S0006-3495(00)76739-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Priebe L., Beuckelmann D. J. Simulation study of cellular electric properties in heart failure. Circ Res. 1998 Jun 15;82(11):1206–1223. doi: 10.1161/01.res.82.11.1206. [DOI] [PubMed] [Google Scholar]
  55. Rice J. J., Jafri M. S., Winslow R. L. Modeling gain and gradedness of Ca2+ release in the functional unit of the cardiac diadic space. Biophys J. 1999 Oct;77(4):1871–1884. doi: 10.1016/s0006-3495(99)77030-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Rose W. C., Balke C. W., Wier W. G., Marban E. Macroscopic and unitary properties of physiological ion flux through L-type Ca2+ channels in guinea-pig heart cells. J Physiol. 1992 Oct;456:267–284. doi: 10.1113/jphysiol.1992.sp019336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sah Rajan, Ramirez Rafael J., Backx Peter H. Modulation of Ca(2+) release in cardiac myocytes by changes in repolarization rate: role of phase-1 action potential repolarization in excitation-contraction coupling. Circ Res. 2002 Feb 8;90(2):165–173. doi: 10.1161/hh0202.103315. [DOI] [PubMed] [Google Scholar]
  58. Santana L. F., Cheng H., Gómez A. M., Cannell M. B., Lederer W. J. Relation between the sarcolemmal Ca2+ current and Ca2+ sparks and local control theories for cardiac excitation-contraction coupling. Circ Res. 1996 Jan;78(1):166–171. doi: 10.1161/01.res.78.1.166. [DOI] [PubMed] [Google Scholar]
  59. Schröder F., Handrock R., Beuckelmann D. J., Hirt S., Hullin R., Priebe L., Schwinger R. H., Weil J., Herzig S. Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle. Circulation. 1998 Sep 8;98(10):969–976. doi: 10.1161/01.cir.98.10.969. [DOI] [PubMed] [Google Scholar]
  60. Sham J. S. Ca2+ release-induced inactivation of Ca2+ current in rat ventricular myocytes: evidence for local Ca2+ signalling. J Physiol. 1997 Apr 15;500(Pt 2):285–295. doi: 10.1113/jphysiol.1997.sp022020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sham J. S., Cleemann L., Morad M. Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes. Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):121–125. doi: 10.1073/pnas.92.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sham J. S., Song L. S., Chen Y., Deng L. H., Stern M. D., Lakatta E. G., Cheng H. Termination of Ca2+ release by a local inactivation of ryanodine receptors in cardiac myocytes. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15096–15101. doi: 10.1073/pnas.95.25.15096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Shannon T. R., Ginsburg K. S., Bers D. M. Reverse mode of the sarcoplasmic reticulum calcium pump and load-dependent cytosolic calcium decline in voltage-clamped cardiac ventricular myocytes. Biophys J. 2000 Jan;78(1):322–333. doi: 10.1016/S0006-3495(00)76595-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sipido K. R., Callewaert G., Carmeliet E. Inhibition and rapid recovery of Ca2+ current during Ca2+ release from sarcoplasmic reticulum in guinea pig ventricular myocytes. Circ Res. 1995 Jan;76(1):102–109. doi: 10.1161/01.res.76.1.102. [DOI] [PubMed] [Google Scholar]
  65. Smith G. D., Keizer J. E., Stern M. D., Lederer W. J., Cheng H. A simple numerical model of calcium spark formation and detection in cardiac myocytes. Biophys J. 1998 Jul;75(1):15–32. doi: 10.1016/S0006-3495(98)77491-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Soeller C., Cannell M. B. Numerical simulation of local calcium movements during L-type calcium channel gating in the cardiac diad. Biophys J. 1997 Jul;73(1):97–111. doi: 10.1016/S0006-3495(97)78051-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Song L. S., Sham J. S., Stern M. D., Lakatta E. G., Cheng H. Direct measurement of SR release flux by tracking 'Ca2+ spikes' in rat cardiac myocytes. J Physiol. 1998 Nov 1;512(Pt 3):677–691. doi: 10.1111/j.1469-7793.1998.677bd.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Song L. S., Wang S. Q., Xiao R. P., Spurgeon H., Lakatta E. G., Cheng H. beta-Adrenergic stimulation synchronizes intracellular Ca(2+) release during excitation-contraction coupling in cardiac myocytes. Circ Res. 2001 Apr 27;88(8):794–801. doi: 10.1161/hh0801.090461. [DOI] [PubMed] [Google Scholar]
  69. Stern M. D., Song L. S., Cheng H., Sham J. S., Yang H. T., Boheler K. R., Ríos E. Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors. J Gen Physiol. 1999 Mar;113(3):469–489. doi: 10.1085/jgp.113.3.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Stern M. D. Theory of excitation-contraction coupling in cardiac muscle. Biophys J. 1992 Aug;63(2):497–517. doi: 10.1016/S0006-3495(92)81615-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Sun L., Fan J. S., Clark J. W., Palade P. T. A model of the L-type Ca2+ channel in rat ventricular myocytes: ion selectivity and inactivation mechanisms. J Physiol. 2000 Nov 15;529(Pt 1):139–158. doi: 10.1111/j.1469-7793.2000.00139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Tseng G. N., Robinson R. B., Hoffman B. F. Passive properties and membrane currents of canine ventricular myocytes. J Gen Physiol. 1987 Nov;90(5):671–701. doi: 10.1085/jgp.90.5.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Valdivia H. H., Kaplan J. H., Ellis-Davies G. C., Lederer W. J. Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation. Science. 1995 Mar 31;267(5206):1997–2000. doi: 10.1126/science.7701323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Wagner J., Keizer J. Effects of rapid buffers on Ca2+ diffusion and Ca2+ oscillations. Biophys J. 1994 Jul;67(1):447–456. doi: 10.1016/S0006-3495(94)80500-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Wang S. Q., Song L. S., Lakatta E. G., Cheng H. Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells. Nature. 2001 Mar 29;410(6828):592–596. doi: 10.1038/35069083. [DOI] [PubMed] [Google Scholar]
  76. Wier W. G., Balke C. W. Ca(2+) release mechanisms, Ca(2+) sparks, and local control of excitation-contraction coupling in normal heart muscle. Circ Res. 1999 Oct 29;85(9):770–776. doi: 10.1161/01.res.85.9.770. [DOI] [PubMed] [Google Scholar]
  77. Wier W. G., Egan T. M., López-López J. R., Balke C. W. Local control of excitation-contraction coupling in rat heart cells. J Physiol. 1994 Feb 1;474(3):463–471. doi: 10.1113/jphysiol.1994.sp020037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Winslow R. L., Rice J., Jafri S., Marbán E., O'Rourke B. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, II: model studies. Circ Res. 1999 Mar 19;84(5):571–586. doi: 10.1161/01.res.84.5.571. [DOI] [PubMed] [Google Scholar]
  79. Yue D. T., Marban E. Permeation in the dihydropyridine-sensitive calcium channel. Multi-ion occupancy but no anomalous mole-fraction effect between Ba2+ and Ca2+. J Gen Physiol. 1990 May;95(5):911–939. doi: 10.1085/jgp.95.5.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Zahradníková A., Zahradník I. A minimal gating model for the cardiac calcium release channel. Biophys J. 1996 Dec;71(6):2996–3012. doi: 10.1016/S0006-3495(96)79492-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Zahradníková A., Zahradník I., Györke I., Györke S. Rapid activation of the cardiac ryanodine receptor by submillisecond calcium stimuli. J Gen Physiol. 1999 Dec;114(6):787–798. doi: 10.1085/jgp.114.6.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Zygmunt A. C. Intracellular calcium activates a chloride current in canine ventricular myocytes. Am J Physiol. 1994 Nov;267(5 Pt 2):H1984–H1995. doi: 10.1152/ajpheart.1994.267.5.H1984. [DOI] [PubMed] [Google Scholar]
  83. Zühlke R. D., Pitt G. S., Deisseroth K., Tsien R. W., Reuter H. Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature. 1999 May 13;399(6732):159–162. doi: 10.1038/20200. [DOI] [PubMed] [Google Scholar]

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