Formation and Maturation of the Calcium Release Apparatus in Developing and Adult Avian Myocardium

Abstract

Muscle fibers release large amounts of calcium from an internal compartment, the sarcoplasmic reticulum (SR), during activation. Two proteins are involved in this process and its control: plasma membrane calcium channels, or dihydropyridine receptors (DHPRs), and SR calcium release channels, or ryanodine receptors (RyRs). The two proteins form part of a structural complex, perhaps unique to muscle cells, which allows an interaction between plasma membrane and SR, resulting in calcium release from the latter. The surface-SR interaction is a step in the coupling between electrical events in the plasma membrane and contraction (excitation-contraction coupling). The structural complexes have been called calcium release units. One key to further understanding the control of calcium homeostasis in muscle is knowledge of how DHPRs and RyRs assemble into calcium release units. We have studied the development of avian myocardium, using immunocytochemistry to locate DHPRs and RyRs and electron microscopy to follow the formation of calcium release units containing feet (RyRs) and large membrane particles (presumably DHPRs). We find that the initial step is a docking of SR vesicles to the plasma membrane, followed by the appearance of feet in the junctional gap between SR and plasma membrane. Feet aggregate in ordered arrays, and the arrays increase in size until they fill the entire junctional gap. Clustering of membrane particles, presumably DHPRs, is apparently coupled to clustering of feet, since the two junction components assemble within patches of membrane of approximately equal size and containing an approximately constant ratio of particles to feet. Thus, despite the fact that no evidence exists for a direct interaction between DHPRs and RyRs in cardiac muscle, some mechanism exists to ensure that the two molecules are clustered in proximity to each other and in the appropriate proportion.

Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans

“…Efficient calcium handling is essential in myocyte organization as the correct t-tubular system orientation is dependent on calcium signaling during development for example [39][40][41]. Therefore, disrupted calcium signaling may predispose to myocyte disarray.…”

The M-band: an elastic web that crosslinks thick filaments in the center of the sarcomere

“…embryonic myocardium [43], possibly compromised by increased calcium sensitivity [40] and/or slower calcium re-uptake owing to immature excitation-contraction coupling [44,45]. As the sarcomere realignment occurs largely during the relaxation phase, this might lead to an increased instability of both sarcomere lengths along the fiber as well as the central position of A-bands.…”

Calcium signalling during excitation-contraction coupling in mammalian atrial myocytes

“…Characterisation of Ca 2+ signalling in ventricular myocytes from animals such as fish (Shiels and White, 2005) has demonstrated that their responses resemble those of mammalian atrial cells. Non-mammalian ventricular cells largely display junctional couplings of VOCCs and RyRs around the cellular periphery (Protasi et al, 1996;Sommer and Jennings, 1992). Peripheral initiation and centripetal propagation is therefore the most commonly observed cardiac Ca 2+ signalling paradigm within biology.…”