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Excitation-contraction coupling in skeletal muscle involves a voltage sensor in the plasma membrane which, in response to depolarization, causes an intracellular calcium-release channel to open. The skeletal isoform of the ryanodine receptor (RyR-1) functions as the Ca2+-release channel and the dihydropyridine receptor (DHPR) functions as the voltage sensor(More)
Ryanodine receptors (RyRs) are present in the endoplasmic reticulum of virtually every cell type and serve critical roles, including excitation-contraction (EC) coupling in muscle cells. In skeletal muscle the primary control of RyR-1 (the predominant skeletal RyR isoform) occurs via an interaction with plasmalemmal dihydropyridine receptors (DHPRs), which(More)
Potassium depolarization of skeletal myotubes evokes slow calcium waves that are unrelated to contraction and involve the cell nucleus (Jaimovich, E., Reyes, R., Liberona, J. L., and Powell, J. A. (2000) Am. J. Physiol. 278, C998-C1010). Studies were done in both the 1B5 (Ry53-/-) murine "dyspedic" myoblast cell line, which does not express any ryanodine(More)
Myotubes expressing wild type RyR1 (WT) or RyR1 with one of three malignant hyperthermia mutations R615C, R2163C, and T4826I (MH) were exposed sequentially to 60 mm KCl in Ca(2+)-replete and Ca(2+)-free external buffers (Ca+ and Ca-, respectively) with 3 min of rest between exposures. Although the maximal peak amplitude of the Ca(2+) transients during K(+)(More)
RyR1 is an intracellular calcium channel with a central role in muscle contraction. We obtained a three-dimensional reconstruction of the RyR1 in the closed state at a nominal resolution of approximately 10 A using cryo-EM. The cytoplasmic assembly consists of a series of interconnected tubular structures that merge into four columns that extend into the(More)
Store-operated Ca(2+) entry (SOCE) occurs in diverse cell types in response to depletion of Ca(2+) within the endoplasmic/sarcoplasmic reticulum and functions both to refill these stores and to shape cytoplasmic Ca(2+) transients. Here we report that in addition to conventional SOCE, skeletal myotubes display a physiological mechanism that we term(More)
Maurocalcine (MCa) isolated from Scorpio maurus palmatus venom shares 82% sequence identity with imperatoxin A. Both scorpion toxins are putative mimics of the II-III loop peptide (termed peptide A (pA)) of alpha(1s)-dihydropyridine receptor and are thought to act at a common site on ryanodine receptor type 1 (RyR1) important for skeletal muscle EC(More)
In muscle cells, excitation-contraction (e-c) coupling is mediated by "calcium release units," junctions between the sarcoplasmic reticulum (SR) and exterior membranes. Two proteins, which face each other, are known to functionally interact in those structures: the ryanodine receptors (RyRs), or SR calcium release channels, and the dihydropyridine receptors(More)
The 12 kDa FK506-binding protein (FKBP12) constitutively binds to the calcium release channel RyR1. Removal of FKBP12 using FK506 or rapamycin causes an increased open probability and an increase in the frequency of sub-conductance states in RyR1. Using cryo-electron microscopy and single-particle image processing, we have determined the 3D difference map(More)