Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A peptide corresponding to residues 681-690 of the II-III loop of the skeletal muscle dihydropyridine receptor alpha(1) subunit (DHPR, alpha(1S)) has been reported to activate the skeletal muscle ryanodine receptor (RyR1) in vitro. Within this region of alpha(1S), a cluster of basic residues, Arg(681)-Lys(685), was previously reported to be indispensable for the activation of RyR1 in microsomal preparations and lipid bilayers. We have used an intact alpha(1S) subunit with scrambled sequence in this region of the II-III loop (alpha(1S)-scr) to test the importance of residues 681-690 and the basic motif for skeletal-type excitation-contraction (EC) coupling and retrograde signaling in vivo. When expressed in dysgenic myotubes (which lack endogenous alpha(1S)), alpha(1S)-scr restored calcium currents that were indistinguishable, in current density and voltage dependence, from those restored by wild-type alpha(1S). The scrambled DHPR also rescued skeletal-type EC coupling, as indicated by electrically evoked contractions in the presence of 0.5 mm Cd(2+) and 0.1 mm La(3+). Furthermore, the release of intracellular Ca(2+), as assayed by the indicator dye, Fluo-3, had similar kinetics and voltage dependence for alpha(1S) and alpha(1S)-scr. These data suggest that residues 681-690 of the alpha(1S) II-III loop are not essential in muscle cells for normal functioning of the DHPR, including skeletal-type EC coupling and retrograde signaling.
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PMID:Excitation-contraction coupling is not affected by scrambled sequence in residues 681-690 of the dihydropyridine receptor II-III loop. 1091 79

The beta1a subunit of the skeletal muscle voltage-gated Ca2+ channel plays a fundamental role in the targeting of the channel to the tubular system as well as in channel function. To determine whether this cytosolic auxiliary subunit is also a regulatory protein of Ca2+ release from the sarcoplasmic reticulum in vivo, we pressure-injected the beta1a subunit into intact adult mouse muscle fibers and recorded, with Fluo-3 AM, the intracellular Ca2+ signal induced by the action potential. We found that the beta1a subunit significantly increased, within minutes, the amplitude of Ca2+ release without major changes in its time course. beta1a subunits with the carboxy-terminus region deleted did not show an effect on Ca2+ release. The possibility that potentiation of Ca2+ release is due to a direct interaction between the beta1a subunit and the ryanodine receptor was ruled out by bilayer experiments of RyR1 single-channel currents and also by Ca2+ flux experiments. Our data suggest that the beta1a subunit is capable of regulating E-C coupling in the short term and that the integrity of the carboxy-terminus region is essential for its modulatory effect.
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PMID:Short-term regulation of excitation-contraction coupling by the beta1a subunit in adult mouse skeletal muscle. 1618 88