Functional equivalence of dihydropyridine receptor a1S and b1a subunits in triggering excitation-contraction coupling in skeletal muscle

Coronado, Roberto; Ahern, Chris; Sheridan, David C.; Cheng, Weijun; Carbonneau, Leah; Bhattacharya, Dipankar

doi:10.4067/s0716-97602004000400010

Cited by 33 publications

(30 citation statements)

References 56 publications

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“…Thus, the ␤ 1a -induced facilitation of ␣ 1S charge movement was not detected in the mouse system and consequently experimental attempts on the ultrastructural level were not pushed forward (14,17,18). Due to the lack of these essential informations, the data of a large series of ␤-expression experiments (24, 25, 49 -52) were in general interpreted in a way that domains of the DHPR ␤ 1a subunit, similar to elements present in the ␣ 1S subunit, might be directly involved in activation of RyR1 channels (26).…”

Section: Discussionmentioning

confidence: 99%

“…Previous reconstitution studies made in the ␤ 1 -null mouse system (24, 25) using different ␤ subunit constructs (26) did not allow differentiation between ␤-induced enhancement of non-functional ␣ 1S membrane expression and the facilitation of ␣ 1S charge movement, due to the lack of information on ␣ 1S triad expression levels. Furthermore, the ␤-induced arrangement of DHPRs in tetrads was not detected as no ultrastructural information was obtained.…”

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confidence: 99%

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Proper Restoration of Excitation-Contraction Coupling in the Dihydropyridine Receptor β1-null Zebrafish Relaxed Is an Exclusive Function of the β1a Subunit

Schredelseker

Dayal

Schwerte

et al. 2009

Journal of Biological Chemistry

100

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The paralyzed zebrafish strain relaxed carries a null mutation for the skeletal muscle dihydropyridine receptor (DHPR) ␤ 1a subunit. Lack of ␤ 1a results in (i) reduced membrane expression of the pore forming DHPR ␣ 1S subunit, (ii) elimination of ␣ 1S charge movement, and (iii) impediment of arrangement of the DHPRs in groups of four (tetrads) opposing the ryanodine receptor (RyR1), a structural prerequisite for skeletal muscletype excitation-contraction (EC) coupling. In this study we used relaxed larvae and isolated myotubes as expression systems to discriminate specific functions of ␤ 1a from rather general functions of ␤ isoforms. Zebrafish and mammalian ␤ 1a subunits quantitatively restored ␣ 1S triad targeting and charge movement as well as intracellular Ca 2؉ release, allowed arrangement of DHPRs in tetrads, and most strikingly recovered a fully motile phenotype in relaxed larvae. Interestingly, the cardiac/neuronal ␤ 2a as the phylogenetically closest, and the ancestral housefly ␤ M as the most distant isoform to ␤ 1a also completely recovered ␣ 1S triad expression and charge movement. However, both revealed drastically impaired intracellular Ca 2؉ transients and very limited tetrad formation compared with ␤ 1a . Consequently, larval motility was either only partially restored (␤ 2a -injected larvae) or not restored at all (␤ M ). Thus, our results indicate that triad expression and facilitation of 1,4-dihydropyridine receptor (DHPR) charge movement are common features of all tested ␤ subunits, whereas the efficient arrangement of DHPRs in tetrads and thus intact DHPR-RyR1 coupling is only promoted by the ␤ 1a isoform. Consequently, we postulate a model that presents ␤ 1a as an allosteric modifier of ␣ 1S conformation enabling skeletal muscle-type EC coupling. Excitation-contraction (EC)3 coupling in skeletal muscle is critically dependent on the close interaction of two distinct Ca 2ϩ channels. Membrane depolarizations of the myotube are sensed by the voltage-dependent 1,4-dihydropyridine receptor (DHPR) in the sarcolemma, leading to a rearrangement of charged amino acids (charge movement) in the transmembrane segments S4 of the pore-forming DHPR ␣ 1S subunit (1, 2). This conformational change induces via protein-protein interaction (3, 4) the opening of the sarcoplasmic type-1 ryanodine receptor (RyR1) without need of Ca 2ϩ influx through the DHPR (5). The release of Ca 2ϩ from the sarcoplasmic reticulum via RyR1 consequently induces muscle contraction. The protein-protein interaction mechanism between DHPR and RyR1 requires correct ultrastructural targeting of both channels. In Ca 2ϩ release units (triads and peripheral couplings) of the skeletal muscle, groups of four DHPRs (tetrads) are coupled to every other RyR1 and hence are geometrically arranged following the RyR-specific orthogonal arrays (6).The skeletal muscle DHPR is a heteromultimeric protein complex, composed of the voltage-sensing and pore-forming ␣ 1S subunit and auxiliary subunits ␤ 1a , ␣ 2 ␦-1, and ␥ 1 (7). While gene knock-out of t...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Proper Restoration of Excitation-Contraction Coupling in the Dihydropyridine Receptor β1-null Zebrafish Relaxed Is an Exclusive Function of the β1a Subunit

Schredelseker

Dayal

Schwerte

et al. 2009

Journal of Biological Chemistry

100

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“…First, the molecular machinery for such coupling is present in these terminals. Patch-clamp studies revealed L-type Ca 2ϩ channels in the terminals (Lemos and Nowycky, 1989;Wang et al, 1997Wang et al, , 1999, and cDNA microarrays studies have shown (Mutsuga et al, 2004) that magnocellular neurons in rat express the same DHPR isoform (␣ 1S ) coupled to type 1 RyRs in skeletal muscle (Coronado et al, 2004). In neurons, L-type calcium channels are almost always present but typically contribute only a minor fraction of the overall highthreshold current (Bean and Mintz, 1994;Wang et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Dihydropyridine Receptors and Type 1 Ryanodine Receptors Constitute the Molecular Machinery for Voltage-Induced Ca²⁺Release in Nerve Terminals

et al. 2006

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“…The ␤ 1a subunit is a soluble protein which binds to ␣ 1S and promotes its membrane trafficking (18). Moreover, ␤ 1a is coequal in importance with the ␣ 1S II-III loop for tetrad formation (19) and skeletal EC coupling (20,21). Among the possible explanations for these results is that ␤ 1a and/or the II-III loop bind to RyR1, perhaps in close proximity to one another.…”

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confidence: 96%

Fluorescence Resonance Energy Transfer (FRET) Indicates That Association with the Type I Ryanodine Receptor (RyR1) Causes Reorientation of Multiple Cytoplasmic Domains of the Dihydropyridine Receptor (DHPR) α1S Subunit

Polster

Ohrtman

Beam

et al. 2012

Journal of Biological Chemistry

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Functional equivalence of dihydropyridine receptor a1S and b1a subunits in triggering excitation-contraction coupling in skeletal muscle

Cited by 33 publications

References 56 publications

Proper Restoration of Excitation-Contraction Coupling in the Dihydropyridine Receptor β1-null Zebrafish Relaxed Is an Exclusive Function of the β1a Subunit

Proper Restoration of Excitation-Contraction Coupling in the Dihydropyridine Receptor β1-null Zebrafish Relaxed Is an Exclusive Function of the β1a Subunit

Dihydropyridine Receptors and Type 1 Ryanodine Receptors Constitute the Molecular Machinery for Voltage-Induced Ca²⁺Release in Nerve Terminals

Fluorescence Resonance Energy Transfer (FRET) Indicates That Association with the Type I Ryanodine Receptor (RyR1) Causes Reorientation of Multiple Cytoplasmic Domains of the Dihydropyridine Receptor (DHPR) α1S Subunit

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Functional equivalence of dihydropyridine receptor a1S and b1a subunits in triggering excitation-contraction coupling in skeletal muscle

Cited by 33 publications

References 56 publications

Proper Restoration of Excitation-Contraction Coupling in the Dihydropyridine Receptor β1-null Zebrafish Relaxed Is an Exclusive Function of the β1a Subunit

Proper Restoration of Excitation-Contraction Coupling in the Dihydropyridine Receptor β1-null Zebrafish Relaxed Is an Exclusive Function of the β1a Subunit

Dihydropyridine Receptors and Type 1 Ryanodine Receptors Constitute the Molecular Machinery for Voltage-Induced Ca2+Release in Nerve Terminals

Fluorescence Resonance Energy Transfer (FRET) Indicates That Association with the Type I Ryanodine Receptor (RyR1) Causes Reorientation of Multiple Cytoplasmic Domains of the Dihydropyridine Receptor (DHPR) α1S Subunit

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Dihydropyridine Receptors and Type 1 Ryanodine Receptors Constitute the Molecular Machinery for Voltage-Induced Ca²⁺Release in Nerve Terminals