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?1a490-508, a 19-residue peptide from C-terminal tail of Cav1.1 ?1a subunit, potentiates voltage-dependent calcium release in adult skeletal muscle fibers.

ABSTRACT: The ?1 and ?1a subunits of the skeletal muscle calcium channel, Cav1.1, as well as the Ca(2+) release channel, ryanodine receptor (RyR1), are essential for excitation-contraction coupling. RyR1 channel activity is modulated by the ?1a subunit and this effect can be mimicked by a peptide (?1a490-524) corresponding to the 35-residue C-terminal tail of the ?1a subunit. Protein-protein interaction assays confirmed a high-affinity interaction between the C-terminal tail of the ?1a and RyR1. Based on previous results using overlapping peptides tested on isolated RyR1, we hypothesized that a 19-amino-acid residue peptide (?1a490-508) is sufficient to reproduce activating effects of ?1a490-524. Here we examined the effects of ?1a490-508 on Ca(2+) release and Ca(2+) currents in adult skeletal muscle fibers subjected to voltage-clamp and on RyR1 channel activity after incorporating sarcoplasmic reticulum vesicles into lipid bilayers. ?1a490-508 (25 nM) increased the peak Ca(2+) release flux by 49% in muscle fibers. Considerably fewer activating effects were observed using 6.25, 100, and 400 nM of ?1a490-508 in fibers. ?1a490-508 also increased RyR1 channel activity in bilayers and Cav1.1 currents in fibers. A scrambled form of ?1a490-508 peptide was used as negative control and produced negligible effects on Ca(2+) release flux and RyR1 activity. Our results show that the ?1a490-508 peptide contains molecular components sufficient to modulate excitation-contraction coupling in adult muscle fibers.

SUBMITTER: Hernandez-Ochoa EO

PROVIDER: S-EPMC3944469 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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β1a490-508, a 19-residue peptide from C-terminal tail of Cav1.1 β1a subunit, potentiates voltage-dependent calcium release in adult skeletal muscle fibers.

Hernández-Ochoa Erick O EO Olojo Rotimi O RO Rebbeck Robyn T RT Dulhunty Angela F AF Schneider Martin F MF

Biophysical journal 20140201 3

The α1 and β1a subunits of the skeletal muscle calcium channel, Cav1.1, as well as the Ca(2+) release channel, ryanodine receptor (RyR1), are essential for excitation-contraction coupling. RyR1 channel activity is modulated by the β1a subunit and this effect can be mimicked by a peptide (β1a490-524) corresponding to the 35-residue C-terminal tail of the β1a subunit. Protein-protein interaction assays confirmed a high-affinity interaction between the C-terminal tail of the β1a and RyR1. Based on ...[more]

PMID: 24507594

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Dataset Information

?1a490-508, a 19-residue peptide from C-terminal tail of Cav1.1 ?1a subunit, potentiates voltage-dependent calcium release in adult skeletal muscle fibers.

Publications

β1a490-508, a 19-residue peptide from C-terminal tail of Cav1.1 β1a subunit, potentiates voltage-dependent calcium release in adult skeletal muscle fibers.

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