Ca2+ sparks involving multiple Ca2+ release sites along Z‐lines in rat heart cells.

Parker, Ian; Zang, Wei-Jin; Wier, W. Gil

doi:10.1113/jphysiol.1996.sp021747

Cited by 142 publications

(149 citation statements)

References 17 publications

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“…2C), whereas the rest is occupied by other organelles such as mitochondria (12). Because diffusion depends on the gradient and the projected area through which diffusion occurs (Fick's first law), our data can explain the unexpected observation that, in the rat, the apparent diffusion coefficient for Ca 2ϩ during a Ca 2ϩ spark is twice as large in the longitudinal direction compared with the transverse direction (19). For saltatory wave propagation between RyR clusters, the velocity should be proportional to D/d, where D is the apparent diffusion coefficient and d is a mean distance between release sites (20).…”

Section: Discussionsupporting

confidence: 62%

“…For saltatory wave propagation between RyR clusters, the velocity should be proportional to D/d, where D is the apparent diffusion coefficient and d is a mean distance between release sites (20). From our measurements, the longitudinal spacing of release sites in the rat is Ϸ1.8 m, and the geometric mean transverse spacing is 0.8 m. From Ca 2ϩ spark properties, the apparent longitudinal and transverse diffusion coefficient are 7.9 and 17.1 m 2 /s, respectively (19). Therefore the ratio of transverse-to-longitudinal wave propagation velocity should be 7.9/0.8 to 17.1/1.8 (respectively) or 1.04, i.e., close to unity.…”

Section: Discussionmentioning

confidence: 96%

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Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

Soeller¹,

Crossman²,

Gilbert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

145

183

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Single rat ventricular myocytes and human ventricle tissue sections were labeled with antibodies against the ryanodine receptor (RyR) and ␣-actinin to examine the 3D distribution of RyRs with confocal microscopy. Image contrast was maximized by refractive index matching and deconvolution. The RyR label formed discrete puncta representing clusters of RyRs or ''couplons'' around the edges of the myofilaments with a nearest-neighbor spacing of 0.66 ؎ 0.06 m in rat and 0.78 ؎ 0.07 m in human. Each bundle of myofibrils was served by approximately six couplons, which supplied a cross-sectional area of Ϸ0.6 m 2 in rat and Ϸ0.8 m 2 in human. Although the couplons were in reasonable registration with zlines, there were discontinuities in the longitudinal position of sarcomeres so that dislocations in the order of RyR clusters occurred. There was Ϸ53% longitudinal registration of RyR clusters, suggesting a nonrandom placement of couplons around the sarcomere. These data can explain the spherical propagation of Ca 2؉ waves and provide quantitative 3D data sets needed for accurate modeling of cardiac Ca 2؉ -induced Ca 2؉ release. By quantifying labeling intensity in rat ventricular myocytes, a lower limit of 78 RyRs per cluster (on average) was obtained. By modeling the couplon as a disk wrapping around a t-tubule and fitting cluster images, 95% of couplons contained between 120 and 260 RyRs (assuming that RyRs are tight packed with a spacing of 29 nm). Assuming similar labeling efficiency in human, from the fluorescence intensity alone we estimate that human ventricular myocytes contain Ϸ30% fewer RyRs per couplon than rat.calcium-induced calcium release ͉ excitation-contraction coupling ͉ sarcoplasmic reticulum I n cardiac ventricular muscle, excitation-contraction (EC) coupling arises from Ca 2ϩ release via clusters of ryanodine receptors (RyRs) in regions of close apposition between the sarcoplasmic reticulum (SR) and surface membranes in functional units called couplons (1, 2). Current work directed at understanding cardiac EC coupling is hindered by uncertainty in the size and 3D distribution of the couplons. Previous detailed analysis from electron micrographs has shown that typically 30-270 RyRs (depending on species) may be present in a couplon (1), but the thin sectioning associated with EM limits analysis of the spatial relationship between nearby and more distant couplons. Such knowledge is important, not only to make sense of the structures that underlie Ca 2ϩ sparks (3, 4) but also for detailed mathematical modeling of cardiac Ca 2ϩ metabolism.In this study, we have used immunocytochemistry combined with 3D imaging and analysis to both reveal the 3D organization of RyR clusters and estimate the numbers of RyRs within the couplon. Our analyses generally support some detailed quantitative measurements from EM (1), but also provide insight into organization in 3D at spatial scales that would be extremely laborious (if not impossible) to achieve by using conventional thin sectioning. In addition, the antibody labe...

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 96%

Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

Soeller¹,

Crossman²,

Gilbert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

145

183

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“…By showing the existence of events smaller than sparks, the present results indirectly suggest that sparks involve multiple channels in skeletal muscle. They also add, albeit indirectly, to the body of increasing evidence (Lipp & Niggli, 1996;Parker, Zang & Wier, 1996;Blatter, H user & R úos, 1997) that cardiac muscle sparks, which are larger and last longer than skeletal muscle sparks, also reflect activation of multiple release channels.…”

Section: Discussionmentioning

confidence: 99%

Small event Ca²⁺ release: a probable precursor of Ca²⁺ sparks in frog skeletal muscle

Shirokova

Rı́os

1997

The Journal of Physiology

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Fluo‐3 fluorescence associated with Ca2+ release was recorded with confocal microscopy in single muscle fibres. Clamp depolarization to −65 or −60 mV elicited Ca2+ sparks with amplitudes and spatial widths distributed approximately normally, with mean values of 0.79 of resting fluorescence and 0.8 μm (S.D., 0.17 and 0.2 μm; n= 193), respectively. Given these distributions, events of amplitude less than 0.45 or width less than 0.4 μm are unlikely to be sparks. Low voltage depolarization (−72 mV) elicited only one spark per triad every 6 s, but generated a relative increase in fluorescence at triads of 0.05. This increase must therefore have been due to events smaller than sparks. The variance/mean ratio of triadic fluorescence gradients averaged 0.11 at low voltages and increased severalfold at the higher voltages at which sparks appeared, indicating the existence of at least two event amplitudes. Tetracaine (200 μm) reversibly abolished sparks and the early peak of Ca2+ release at all voltages. In its presence, discrete events were smaller than the spark criterion, and triadic gradients had a variance/mean ratio of 0.11. The phenylalkylamine D600 (2 μm) reduced release at all voltages, abolishing sparks and the peak of Ca2+ release at low but not at high voltages. The parallel abolition of all sparks and the peak of Ca2+ release indicates that both phenomena are activated by Ca2+. The restoration of sparks by voltage in D600 suggests that release in small events provides the trigger Ca2+ for activation of sparks.

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“…Recent investigations have shown that localized and spontaneous intracellular calcium release events (i.e., calcium sparks) also arise from calcium release through ryanodine receptor channels in skeletal, cardiac, and smooth muscle cells (14)(15)(16)(17)(18)(19)(20). In porcine ASM cells, earlier studies revealed occurrence of calcium sparks that were grouped and coupled across adjacent regions of the cell (16).…”

Section: Spontaneous Calcium Release Events In Airway Smooth Muscle Cmentioning

confidence: 99%

Calcium Signaling in Airway Smooth Muscle

Jude¹,

Wylam²,

Walseth³

et al. 2008

Proceedings of the American Thoracic Society

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Contractility of airway smooth muscle requires elevation of intracellular calcium concentration. Under resting conditions, airway smooth muscle cells maintain a relatively low intracellular calcium concentration, and activation of the surface receptors by contractile agonists results in an elevation of intracellular calcium, culminating in contraction of the cell. The pattern of elevation of intracellular calcium brought about by agonists is a dynamic process and involves the coordinated activities of ion channels located in the plasma membrane and the sarcoplasmic reticulum. Among the signaling molecules involved in this dynamic calcium regulation in airway smooth muscle cells are inositol 1,4,5-trisphosphate and cyclic ADPribose, which mobilize calcium from the sarcoplasmic reticulum by acting via the inositol 1,4,5-trisphosphate and ryanodine receptors, respectively. In addition, calcium influx from the extracellular space is critical for the repletion of the intracellular calcium stores during activation of the cells by agonists. Calcium influx can occur via voltage-and receptor-gated channels in the plasma membrane, as well as by influx that is triggered by depletion of the intracellular stores (i.e., store-operated calcium entry mechanism). Transient receptor potential proteins appear to mediate the calcium influx via receptor-and store-operated channels. Recent studies have shown that proinflammatory cytokines regulate the expression and activity of the pathways involved in intracellular calcium regulation, thereby contributing to airway smooth muscle cell hyperresponsiveness. In this review, we will discuss the specific roles of cyclic ADP-ribose/ryanodine receptor channels and transient receptor potential channels in the regulation of intracellular calcium in airway smooth muscle cells. DYNAMIC INTRACELLULAR CALCIUM REGULATION IN AIRWAY SMOOTH MUSCLE CELLSExposure of airway smooth muscle (ASM) cells to contractile agonists results in a biphasic elevation of intracellular calcium concentration ([Ca 21 ] i ) that is characterized by an initial rapid and transient rise in calcium, followed by a decline to a lower, sustained steady-state concentration above the basal level (1-3). This biphasic [Ca 21 ] i response results from calcium influx from the extracellular space and release of calcium from the intracellular stores (i.e., the sarcoplasmic reticulum [SR]). Earlier studies have attributed the initial rapid and transient phase of the [Ca 21 ] i response to release from the SR, while the sustained phase of the response was thought to be due to influx from the extracellular space (2-6). Recent investigations using the improved temporal and spatial resolution features of real-time confocal microscopy have shed light on the dynamics of the [Ca 21 ] i response in ASM cells. These studies have shown that the biphasic [Ca 21 ] i response of ASM cells elicited by contractile agonists in reality consists of propagating regenerative calcium oscillations that originate at a location within a cell and propagate...

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Ca2+ sparks involving multiple Ca2+ release sites along Z‐lines in rat heart cells.

Cited by 142 publications

References 17 publications

Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

Small event Ca²⁺ release: a probable precursor of Ca²⁺ sparks in frog skeletal muscle

Calcium Signaling in Airway Smooth Muscle

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Ca2+ sparks involving multiple Ca2+ release sites along Z‐lines in rat heart cells.

Cited by 142 publications

References 17 publications

Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

Small event Ca2+ release: a probable precursor of Ca2+ sparks in frog skeletal muscle

Calcium Signaling in Airway Smooth Muscle

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Product

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Small event Ca²⁺ release: a probable precursor of Ca²⁺ sparks in frog skeletal muscle