Role of the Diadic Cleft in Myocardial Contractile Control
1997; Lippincott Williams & Wilkins; Volume: 96; Issue: 10 Linguagem: Inglês
10.1161/01.cir.96.10.3761
ISSN1524-4539
Autores Tópico(s)Cardiac pacing and defibrillation studies
ResumoHomeCirculationVol. 96, No. 10Role of the Diadic Cleft in Myocardial Contractile Control Free AccessResearch ArticleDownload EPUBAboutView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticleDownload EPUBRole of the Diadic Cleft in Myocardial Contractile Control G.A. Langer and A. Peskoff G.A. LangerG.A. Langer From the Departments of Physiology and Medicine, Cardiovascular Research Laboratory, UCLA Center for Health Sciences, Los Angeles, Calif. and A. PeskoffA. Peskoff From the Departments of Physiology and Medicine, Cardiovascular Research Laboratory, UCLA Center for Health Sciences, Los Angeles, Calif. Originally published18 Nov 1997https://doi.org/10.1161/01.CIR.96.10.3761Circulation. 1997;96:3761–3765The diadic cleft space is the region of the cell, in mammalian heart, between the JSR membrane and the inner leaflet of the T-tubular SL membrane. As results accumulate from various laboratories, the role of the cleft region in regulation of the calcium movements of the cell seems to be of considerable significance. Much remains to be learned about the region, but enough is currently known to warrant a brief perspective at this time.Contractile Control: Skeletal and CardiacIn terms of calcium control of contraction, it is useful initially to compare this control in skeletal and cardiac muscle, because both demonstrate cleft structure: diadic in the heart, triadic in skeletal muscle. A simple experiment, which attracted little attention at the time, clearly showed that the process of excitation-contraction coupling is very different in skeletal and heart muscle. Armstrong et al1 showed that single fibers from frog semitendinosus muscle continued to contract for 20 minutes or longer when perfused with zero calcium plus EGTA ([Ca]0 90% of the binding at saturating levels of [Ca]. These sites are inner leaflet phospholipids, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine.27 These phospholipids have not been specifically localized to the clefts, but it is reasonable to suppose at least a homogeneous distribution over the SL, including the clefts. These calcium-binding sites play a critical role in the determination of calcium movements within the cleft space. Fig 2 summarizes the structure of the diadic cleft space. The figure serves only to indicate the most important elements and is not to scale. There is direct experimental support for the inclusion of all components except for the sodium channels, which are shown to enter the space. There is, however, extensive indirect support for sodium channel entry into such a restricted region.293031Calcium Movements in the CleftFrom the preceding review, it seems that the ventricular cell has concentrated Ca2+ and Na+ entry from the extracellular space, Ca2+ entry from its intracellular storage sites (JSR), and Ca2+ exit to the extracellular space, all within the diadic and subsarcolemmal clefts of the cell. Given the SL surface area of a diadic cleft and their T-tubular density,25 it is reasonable to assume a distribution of ≈1 cleft/2 half-sarcomeres. Depending on species and cell size, an average cell would contain ≈10 000 diadic clefts.On the basis of a recently published model19 that includes all the elements of the cleft reviewed above and experimentally measured values for calcium and sodium channel influx, JSR calcium release, and Na+/Ca2+ exchange–mediated calcium efflux, we can outline a possible scenario for the calcium and sodium movements in the cleft space as they might occur over the course of a single cardiac cycle.Calcium Channel InfluxA reasonable assumption for the current through a single calcium channel is that it enters in the form of a 0.3-pA, 1-ms-duration rectangular pulse.32 If the channel is located in the center of an array of 9 feet within the cleft, all 9 feet will be located within a radius of 50 nm from point of the current entry. (Remember that Wibo et al20 found a ratio of 9 feet to 1 calcium channel.) At a distance of 50 nm, [Ca] in the cleft will increase 10 times from its diastolic level of 0.1 to 1 μmol/L within 1.0 ms and increase another 10-fold to 10 μmol/L in the next 1 ms. According to Fabiato,6 an increase of [Ca] to 1 μmol/L in 1.0 ms will trigger a release from the JSR via the feet sufficient to activate ≈50% maximum force; an increase to 4.0 μmol/L in 2 ms will release enough calcium (assuming adequate JSR content) to produce near-maximum force. Therefore, the diadic cleft, where calcium channels are in close juxtaposition to the release channels, is ideally suited as the locus for the process of CICR so elegantly described by Fabiato more than 15 years ago. It is the place where calcium entry and JSR content interact to set the level of calcium release and thereby the level of force development for the cell.Sodium Channel InfluxIn the model, a sodium channel is assumed to deliver sodium at the center of the cleft in a trapezoidal pulse reaching 2 pA within 0.5 ms, remaining at this level for 0.5 ms and then decreasing linearly with time to 0 pA within 0.5 ms.33 This current would produce an increase in cleft [Na] of ≈10 mmol/L (from baseline of ≈12 mmol/L) within 40 nm of the channel entry point for the 0.5 ms that the current is at the 2 pA level. This rise of [Na] in the cleft will cause the Na+/Ca2+ exchanger current to reverse or become outward (net movement of calcium inward) at action potential plateau more positive than 0 mV.34 Therefore, as originally proposed by Leblanc and Hume,29 there would be a transient net movement of calcium into the cell via Na+/Ca2+ exchangers located in the SL of the cleft. The movement would occur for, at most, a few milliseconds when the membrane potential is at its peak positive value. A number of studies3536 indicate that the "reverse" Na+/Ca2+ exchange could serve, under conditions near physiological, to provide the calcium for CICR. Conversely, some studies3738 support the contention that calcium release from the JSR is much more efficiently achieved by calcium entering through the L-type channel. The cleft model19 supports the latter. At best, according to the model, [Ca] would increase to ≈0.5 μmol/L by "reverse exchange" but would require ≈10 ms to do so. This would trigger calcium release capable of producing no more than 20% maximal force.6 Although Na+/Ca2+ exchange in the cleft may or may not contribute to the process of CICR from JSR under physiological conditions, its presence in the cleft is of major importance in calcium efflux from the cell (see below).Calcium Release From JSRAfter calcium entry into the cleft space through the channels, the next step in the excitation-contraction sequence is calcium release from the JSR via the feet. The details of this release (CICR) are not yet established. Stern39 produced a strong theoretical argument against a "common pool" model in which the "trigger" calcium and released calcium are within the same cytosolic pool. This model was not capable of producing a graded release of calcium as is known to occur experimentally. Rather, two types of "local control" were considered possible: (1) One L-type calcium channel directly stimulates one immediately opposed SR calcium- release channel; (2) one L-type channel triggers a regenerative cluster of several SR release channels. Both were capable of producing graded calcium release. There is, indeed, recent experimental evidence40 for close opposition of L-type channel and SR release channels. This study supported the existence of microdomains within the cleft, which included a calcium channel and ryanodine receptors (feet) but excluded Na+/Ca2+ exchangers.It has been difficult to understand why, once release starts from a release channel, it does not become regenerative and continue to put out more and more calcium. Györke and Fill41 have attributed a negative feedback mechanism for shutting down the channel to adaptation rather than inactivation as [Ca] elevates in the vicinity of the SR release channel. It is proposed that open probability peaks and then spontaneously decays (adapts) in the continued presence of elevated calcium. Results from whole cells are consistent with the "adaptation model."424344It should be noted that there is very recent, preliminary evidence that all SR channel release may not be calcium induced. Levi and Ferrier45 report a fraction of SR release dependent only on SL depolarization, a "voltage-activated calcium release." This, of course, is the release mechanism used by skeletal muscle (see above). It seems possible that cardiac muscle might use a combination of CICR and voltage-activated calcium release as well as reverse Na+/Ca2+ exchange.Release of an amount of calcium sufficient to produce maximum force (≈70 μmol/kg wet ventricle) will increase [Ca] in the cleft spaces to >100 μmol/L at the end of a 20-ms release.19 If such release were to occur into a restricted space identical to that depicted in Fig 2, except for removal of the inner leaflet anionic sites, [Ca] would rise to the same high levels during release but return to the 100 nmol/L diastolic level in <1 ms after release ceased. With the anionic calcium-binding sites present, the model indicates that ≈150 ms is required for calcium to diffuse out of the space and for [Ca] in the cleft to return to the 100 nmol/L level. Calcium binding to the large quantity of inner leaflet sites (Fig 2) accounts for the marked diffusional delay. The configuration of experimentally measured individual release events, called calcium "sparks,"46 measured by calcium-sensitive dyes is consistent with the diffusional delay within the clefts as well as, of course, with delays within the cytoplasm.Therefore, the amount of calcium dispersed to the myofilaments depends on the JSR calcium content and the magnitude and rate of calcium entry through the L-type channels. All of the elements involved in this force-determining process are located at the diadic or subsarcolemmal clefts.Na+/Ca2+ ExchangeWe have discussed the role of cleft-based structures in calcium flux through channels and release to the cytoplasm from the JSR. What about removal of calcium from the cell? The major route for this removal is Na+/Ca2+ exchange. It has been shown that a reasonable value for intracellular calcium concentration, [Ca]i, for half-maximal stimulation of the exchangers is ≈5 μmol/L (Kd Ca).47 Depending on the amount of calcium released from the JSR, [Ca]i in the bulk cytoplasm reaches peak levels between 1 and 2 μmol/L for only 30 to 40 ms and then falls to an average level of 60/min, a progressive increase of intracellular calcium would occur. This is inconsistent with long-term cell survival.As discussed earlier, there is considerable evidence to support localization of a large fraction of the Na+/Ca2+ exchangers of the cell in the SL at the cleft spaces. Such placement will greatly enhance the activity of the exchangers during the cardiac cycle. This is because [Ca] in the clefts increases to >100 μmol/L during JSR release (20 ms), but more importantly, the model indicates an average value >5 μmol/L for the next 100 ms. The maintenance of high cleft [Ca] is due largely to the calcium-binding inner leaflet sites, which delay diffusion of calcium from the cleft space (Fig 2). These high [Ca] levels permit the exchangers in the clefts to maintain steady-state intracellular calcium levels in the face of beat rates of ≥300/min. A recent study in which the inner leaflet sites were neutralized showed that there is a markedly decreased calcium efflux from the cells via Na+/Ca2+ exchange.51 This supports the importance of these cleft-based sites in control of calcium efflux from the cell.Therefore, current evidence strongly suggests that calcium influx, calcium storage, calcium release, and calcium efflux are based in cleft-associated structures. The proximity, within the cleft, of the structures involved in these functions seems to make sense in terms of feedback control of cardiac cellular calcium movements and contractility.Selected Abbreviations and AcronymsCICR=calcium-induced calcium releaseDHPR=dihydropyridine receptorJSR=junctional sarcoplasmic reticulumSL=sarcolemma, sarcolemmalT=transverseDownload figureDownload PowerPoint Figure 1. Electron micrograph from rat ventricular muscle. T tubule (TT) is in cross section, and apposed junctional SR is evident. Feet of junction are seen as periodic bridges across space or diadic cleft and indicated by arrows. MIT indicates mitochondrion. Reproduced with permission.10Download figureDownload PowerPoint Figure 2. Schematic of diadic cleft space. Note that region is bounded by SL and JSR. It includes Na+ and Ca2+ channels, Na+/Ca2+ exchangers in SL, and anionic sites (largely phospholipid) at inner SL. Space is spanned by JSR feet from which Ca2+ is released into cleft. Not to scale. Reproduced with permission.19This study was supported by PHS grant HL-28539-13 and the Laubisch and Castera Endowments.FootnotesCorrespondence to Dr G.A. Langer, Departments of Physiology and Medicine, Cardiovascular Research Laboratory, MRL-3645, UCLA Center for Health Sciences, 675 Circle Dr S, Los Angeles, CA 90095-1760. E-mail [email protected] References 1 Armstrong CM, Bezanilla FM, Horowicz P. Twitches in the presence of ethyleneglycolbis (aminoethylether)-N,N′-tetraacetic acid. Biochem Biophys Acta.1972; 267:605-608.CrossrefMedlineGoogle Scholar2 Rich TL, Langer GA, Klassen MG. Two components of coupling calcium in single ventricular cell of rabbits and rats. Am J Physiol.1988; 254:H937-H946.MedlineGoogle Scholar3 Endo M, Tanaka M, Ogawa Y. Calcium-induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibers. Nature.1970; 228:34-36.CrossrefMedlineGoogle Scholar4 Endo M. Calcium release from the sarcoplasmic reticulum. Physiol Rev.1977; 57:71-108.CrossrefMedlineGoogle Scholar5 Fabiato A. Calcium induced release of calcium from cardiac sarcoplasmic reticulum. Am J Physiol.1983; 245:C1-C14.CrossrefMedlineGoogle Scholar6 Fabiato A. Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of skinned canine cardiac Purkinje cell. J Gen Physiol.1985; 85:247-289.CrossrefMedlineGoogle Scholar7 Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature.1987; 328:313-318.CrossrefMedlineGoogle Scholar8 Sommer JR, Johnson EA. Comparative ultrastructure of cardiac cell membrane specializations: a review. Am J Cardiol.1970; 25:184-194.CrossrefMedlineGoogle Scholar9 Forbes MS, Sperelakis N. Myocardial couplings: their structural variations in the mouse. J Ultrastruct Res.1977; 58:50-65.CrossrefMedlineGoogle Scholar10 Frank JS. Ultrastructure of the unfixed myocardial sarcolemma and cell surface. In: Langer GA, ed. Calcium and the Heart. New York, NY: Raven Press; 1990:1-25.Google Scholar11 Furchgott RF, de Gubareff T. Depression of contractile force by ryanodine. Fed Proc.1956; 15:425. Abstract.Google Scholar12 Hillyard IW, Procita L. Action of ryanodine on isolated kitten auricle. Fed Proc.1956; 15:438. Abstract.Google Scholar13 Inui M, Wang S, Saito A, Fleisher S. Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem.1991; 262:1740-1747.Google Scholar14 Inui M, Wang S, Saito A, Fleisher S. Characterization of junctional and longitudinal sarcoplasmic reticulum from heart muscle. J Biol Chem.1988; 263:10843-10850.CrossrefMedlineGoogle Scholar15 Radermacher M, Rao V, Grassucci R, Frank J, Timerman AP, Fleischer S, Wagenknecht T. Cryo-electron microscopy and three dimensional reconstruction of the calcium release channel/ryanodine receptor from skeletal muscle. J Cell Biol.1994; 127:411-423.CrossrefMedlineGoogle Scholar16 Ikemoto N, Antoniu B, Kang JJ, Mészáros LG, Ronjat M. Intracellular calcium transients during calcium release from sarcoplasmic reticulum. Biochemistry.1991; 30:5230-5237.CrossrefMedlineGoogle Scholar17 Jorgensen A, Shen A, Arnold W, McPherson PS, Campbell KP. The Ca2+ release channel/ryanodine receptor is localized in junctional and cellular sarcoplasmic reticulum in cardiac muscle. J Cell Biol.1993; 120:969-980.CrossrefMedlineGoogle Scholar18 Shacklock PS, Wier WG, Balke CW. Local Ca2+ transients (Ca2+ sparks) originate at transverse tubules in rat heart cells. J Physiol.1995; 487:601-608.CrossrefMedlineGoogle Scholar19 Langer GA, Peskoff A. Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell. Biophys J.1996; 70:1169-1182.CrossrefMedlineGoogle Scholar20 Wibo M, Bravo G, Godfraind T. Postnatal maturation of excitation-contraction coupling in rat ventricle in relation to the subcellular localization and surface density of 1,4 hydropyridine and ryanodine receptors. Circ Res.1991; 68:662-673.CrossrefMedlineGoogle Scholar21 Sun X-H, Protasi F, Takahashi M, Takeshima H, Ferguson DG, Franzini-Armstrong C. Molecular architecture of membranes involved in excitation-contraction coupling of cardiac muscle. J Cell Biol.1995; 129:659-671.CrossrefMedlineGoogle Scholar22 Philipson KD. The cardiac Na+-Ca++ exchanger. In: Langer GA, ed. Calcium and the Heart. New York, NY: Raven Press; 1990:85-108.Google Scholar23 Frank JS, Mottino G, Reid D, Molday RS, Philipson KD. Distribution of the Na+/Ca++ exchange protein in mammalian cardiac myocytes: an immuno-fluorescence and immuno-colloidal gold-labeling study. J Cell Biol.1992; 117:337-345.CrossrefMedlineGoogle Scholar24 Chen F, Mottino G, Klitzner TS, Philipson KD, Frank JS. Distribution of the Na+/Ca2+ exchange protein in developing rabbit myocytes. Am J Physiol.1995; 37:C1126-C1132.Google Scholar25 Page E. Quantitative ultrastructural analysis in cardiac membrane physiology. Am J Physiol.1978; 4:C147-C158.CrossrefGoogle Scholar26 Kieval RS, Bloch RJ, Lindenmayer GE, Ambesi A, Lederer WJ. Immunofluorescence localization of the Na-Ca exchanger in heart cells. Am J Physiol.1992; 263:C545-C550.CrossrefMedlineGoogle Scholar27 Post JA, Langer GA, Op den Kamp JAF, Verkleij AJ. Phospholipid asymmetry in cardiac sarcolemma: analysis of intact cells and 'gas dissected' membranes. Biochem Biophys Acta.1988; 943:256-266.CrossrefMedlineGoogle Scholar28 Post JA, Langer GA. Sarcolemmal calcium binding site in heart, I: molecular origin in 'gas-dissected' membranes. J Membr Biol.1992; 129:48-57.Google Scholar29 Leblanc N, Hume JR. Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum. Science.1990; 248:372-376.CrossrefMedlineGoogle Scholar30 Lederer WJ, Niggli E, Hadley RW. Sodium-calcium exchange in excitable cells: fuzzy space. Science.1990; 248:283.CrossrefMedlineGoogle Scholar31 Carmeliet E. A fuzzy subsarcolemmal space for Na+ in cardiac cells? Cardiovasc Res.1992; 26:433-442.CrossrefMedlineGoogle Scholar32 Rose WC, Balke CW, Wier WG, Marban E. Macroscopic and unitary properties of physiological ion flux through L-type Ca channels in guinea-pig heart cells. J Physiol.1992; 456:267-284.CrossrefMedlineGoogle Scholar33 Bohle T, Benndorf K. Multimodal action of single Na+ channels in myocardial mouse cells. Biophys J.1995; 68:121-130.CrossrefMedlineGoogle Scholar34 Matsuoka S, Hilgemann D. Steady state and dynamic properties of cardiac sodium-calcium exchange: ion and voltage dependencies of the transport cycle. J Gen Physiol.1992; 100:963-1001.CrossrefMedlineGoogle Scholar35 Levi A, Spitzer KW, Kohmoto O, Bridge JHB. Depolarization-induced Ca entry via Na-Ca exchange triggers SR release in guinea pig cardiac myocytes. Am J Physiol.1994; 266:H1422-H1433.CrossrefMedlineGoogle Scholar36 Wasserstrom JA, Vites A-M. The role of Na+-Ca2+ exchange in activation of excitation-contraction coupling in rat ventricular myocytes. J Physiol (Lond).1996; 493:529-542.CrossrefGoogle Scholar37 Sham JSK, Cleeman L, Morad M. Gating of the cardiac Ca2+ release channel: the role of Na+ current and Na+-Ca2 exchange. Science.1992; 255:850-853.CrossrefMedlineGoogle Scholar38 Sham JSK, Cleeman L, Morad M. Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes. Proc Natl Acad Sci.1995; 92:121-125.CrossrefMedlineGoogle Scholar39 Stern MD. Theory of excitation-contraction coupling in cardiac muscle. Biophys J.1992; 63:497-517.CrossrefMedlineGoogle Scholar40 Adachi-Akahane S, Cleeman L, Morad M. Cross-signaling between L-type Ca2+ channels and ryanodine receptors in rat ventricular myocytes. J Gen Physiol.1996; 108:435-454.CrossrefMedlineGoogle Scholar41 Györke S, Fill M. Ca+2-induced Ca+2 release in response to flash photolysis. Science.1993; 260:807-809.CrossrefMedlineGoogle Scholar42 Rios E. Reining in Ca2+ release. Biophys J.1994; 67:7-9.CrossrefMedlineGoogle Scholar43 Yasui K, Palade P, Györke S. Negative control mechanism with features of adaption controls Ca2+ release in cardiac myocytes. Biophys J.1994; 61:957-960.Google Scholar44 Györke I, Györke S. Adaptive control of intracellular Ca2+ release in C2C12 mouse myocytes. Pflugers Arch.1996; 431:838-843.CrossrefMedlineGoogle Scholar45 Levi AJ, Ferrier GR. Ca release activated by membrane depolarization in the absence of Ca entry in mammalian heart. Biophys J.1997; 72:A161. Abstract.Google Scholar46 Santana LF, Cheng H, Gomez AM, Cannell MB, Lederer WJ. Relation between the sarcolemmal Ca2+ current and Ca2+ sparks and local control theories for cardiac excitation-contraction coupling. Circ Res.1996; 78:166-171.CrossrefMedlineGoogle Scholar47 Hilgemann DW, Collins A, Matsuoka S. Steady state and dynamic properties of cardiac sodium-calcium exchange: secondary modulation of cytoplasmic calcium and ATP. J Gen Physiol.1992; 100:933-961.CrossrefMedlineGoogle Scholar48 Berlin J, Konishi M. Ca2+ transients in cardiac myocytes measured with high and low affinity Ca2+ indicators. Biophys J.1993; 65:1632-1647.CrossrefMedlineGoogle Scholar49 Bouchard RA, Clark RB, Giles WR. Effects of action potential duration on excitation contraction coupling in rat ventricular myocytes: action potential voltage clamp measurements. Circ Res.1995; 76:790-801.CrossrefMedlineGoogle Scholar50 Bridge JHB, Smolley JR, Spitzer KW. The relationship between charge movements associated with ICa and INa-Ca in cardiac myocytes. Science.1990; 248:376-378.CrossrefMedlineGoogle Scholar51 Wang SY, Peskoff A, Langer GA. Inner sarcolemmal leaflet Ca2+ binding: its role in cardiac Na/Ca exchange. Biophys J.1996; 70:2266-2274.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Shiferaw Y (2016) Nonlinear onset of calcium wave propagation in cardiac cells, Physical Review E, 10.1103/PhysRevE.94.032405, 94:3 Sato D, Bers D, Shiferaw Y and Talkachova A (2013) Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium, PLoS ONE, 10.1371/journal.pone.0085365, 8:12, (e85365) Asfaw M, Alvarez-Lacalle E, Shiferaw Y and Xie L (2013) The Timing Statistics of Spontaneous Calcium Release in Cardiac Myocytes, PLoS ONE, 10.1371/journal.pone.0062967, 8:5, (e62967) Gillespie D and Fill M (2013) Pernicious attrition and inter-RyR2 CICR current control in cardiac muscle, Journal of Molecular and Cellular Cardiology, 10.1016/j.yjmcc.2013.01.011, 58, (53-58), Online publication date: 1-May-2013. Sharma V Mechanisms of Isolated Cell Stimulation Cardiac Bioelectric Therapy, 10.1007/978-0-387-79403-7_10, (221-254) Mahajan A, Shiferaw Y, Sato D, Baher A, Olcese R, Xie L, Yang M, Chen P, Restrepo J, Karma A, Garfinkel A, Qu Z and Weiss J (2008) A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates, Biophysical Journal, 10.1529/biophysj.106.98160, 94:2, (392-410), Online publication date: 1-Jan-2008. Dan P, Lin E, Huang J, Biln P and Tibbits G (2007) Three-Dimensional Distribution of Cardiac Na+-Ca2+ Exchanger and Ryanodine Receptor during Development, Biophysical Journal, 10.1529/biophysj.107.104943, 93:7, (2504-2518), Online publication date: 1-Oct-2007. Gathercole D, Colling D, Skepper J, Takagishi Y, Levi A and Severs N (2000) Immunogold-labeled L-type Calcium Channels are Clustered in the Surface Plasma Membrane Overlying Junctional Sarcoplasmic Reticulum in Guinea-pig Myocytes—Implications for Excitation–contraction Coupling in Cardiac Muscle, Journal of Molecular and Cellular Cardiology, 10.1006/jmcc.2000.1230, 32:11, (1981-1994), Online publication date: 1-Nov-2000. Ponce-Hornos J, Philipson K, Bonazzola P and Langer G (1999) Energetics of Na+–Ca2+ Exchange in Resting Cardiac Muscle, Biophysical Journal, 10.1016/S0006-3495(99)77163-8, 77:6, (3319-3327), Online publication date: 1-Dec-1999. Choi D and Rockman H (1999) β-adrenergic receptor desensitization in cardiac hypertrophy and heart failure, Cell Biochemistry and Biophysics, 10.1007/BF02738246, 31:3, (321-329), Online publication date: 1-Oct-1999. Niggli E (1999) LOCALIZED INTRACELLULAR CALCIUM SIGNALING IN MUSCLE: Calcium Sparks and Calcium Quarks, Annual Review of Physiology, 10.1146/annurev.physiol.61.1.311, 61:1, (311-335), Online publication date: 1-Mar-1999. November 18, 1997Vol 96, Issue 10 Advertisement Article InformationMetrics Copyright © 1997 by American Heart Associationhttps://doi.org/10.1161/01.CIR.96.10.3761 Originally publishedNovember 18, 1997 Keywordscalciumsarcoplasmic reticulumcontractilitymusclesdiadic cleft Advertisement
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