Rapid Confocal Measurements of Ca2+ Sparks in Rat Ventricular Myocytes
The initiation of contraction in mammalian myocardial cells begins with the entry of Ca2+ through sarcolemmal Ca2+ channels (DHP-receptors) and triggering of Ca2+ release from the sarcoplasmic reticulum (SR) via Ca2+ release channels (ryanodine receptors; Näbaueret al., 1989). At the level of optical resolution (0.2–0.5 µm) the functional unit may be perceived as one sarcomere (1.6 to 2.2 tim z-line to z-line) of a single myofibril (diameter = 1 µm). This ”sarcomeric unit“ receives its Ca2+ from a collar of SR which forms dyadic junction with transverse tubules (t-tubules—invaginations of the surface membrane). Below the level of optical resolution, electron microscopy shows that each dyadic junction (0.1 µm diameter, about 30 nm wide) contains a number of DHP receptors in the t-tubular membrane and a larger number of ryanodine receptors opposing them in the SR membrane (Jorgensenet al.,1993; Carlet al., 1995). While there appear to be no mechanical contact between the two types of receptors in cardiac muscle (Sunet al.,1995), it is clear that their communication via rapid local rises in [Ca2+ i (Sham, Cleemann and Morad, 1995; Adachi-Akahane, Cleemann and Morad, 1996) and activation of Ca2+-induced Ca2+ release mechanism (CIRC; Fabiato, 1983, 1985) is of fundamental importance for the control of the cardiac contraction. Yet the details of this control process remains elusive. What is missing, in part, seems to be a clearer understanding of the way the DHP and ryanodine receptors interact in their normal environment. For instance, it is not clear whether the basic Ca2+ signaling unit (Ca2+ µ-domain) is a) a single ryanodine receptor responding to influx of Ca2+ via a single DHP receptor, b) a cluster of ryanodine receptors controlled by one DHP receptor, c) an entire dyadic junction with several DHP and Ryanodine receptors, or even d) an aborted Ca2+ wave spreading over several sarcomeric units.
KeywordsSarcoplasmic Reticulum Ryanodine Receptor Spiral Wave Nuclear Region Optical Resolution
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