scholarly journals Regulation of skeletal ryanodine receptors by dihydropyridine receptor II–III loop C-region peptides: relief of Mg2+ inhibition

2005 ◽  
Vol 387 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Claudia S. HAARMANN ◽  
Angela F. DULHUNTY ◽  
Derek R. LAVER
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Lipid Bilayers ◽  
Surface Membrane ◽  
Ryanodine Receptors ◽  
Dihydropyridine Receptor ◽  
Physical Interaction ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
High Affinity ◽  
Ca2 Channels

The aim of the present study was to explore interactions between surface-membrane DHPR (dihydropyridine receptor) Ca2+ channels and RyR (ryanodine receptor) Ca2+ channels in skeletal-muscle sarcoplasmic reticulum. The C region (725Phe-Pro742) of the linker between the 2nd and 3rd repeats (II–III loop) of the α1 subunit of skeletal DHPRs is essential for skeletal excitation–contraction coupling, which requires a physical interaction between the DHPR and RyR and is independent of external Ca2+. Little is known about the regulatory processes that might take place when the two Ca2+ channels interact. Indeed, interactions between C fragments of the DHPR (C peptides) and RyR have different reported effects on Ca2+ release from the sarcoplasmic reticulum and on RyR channels in lipid bilayers. To gain insight into functional interactions between the proteins and to explore different reported effects, we examined the actions of C peptides on RyR1 channels in lipid bilayers with three key RyR regulators, Ca2+, Mg2+ and ATP. We identified four discrete actions: two novel, low-affinity (>10 μM), rapidly reversible effects (fast inhibition and decreased sensitivity to Mg2+ inhibition) and two slowly reversible effects (high-affinity activation and a slow-onset, low-affinity inhibition). Fast inhibition and high-affinity activation were decreased by ATP. Therefore peptide activation in the presence of ATP and Mg2+, used with Ca2+ release assays, depends on a mechanism different from that seen when Ca2+ is the sole agonist. The relief of Mg2+ inhibition was particularly important since RyR activation during excitation–contraction coupling depends on a similar decrease in Mg2+ inhibition.

Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions

1997 ◽  
Vol 77 (3) ◽  
pp. 699-729 ◽  
Author(s):  
C. Franzini-Armstrong ◽  
F. Protasi
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Striated Muscle ◽  
Surface Membrane ◽  
Ryanodine Receptors ◽  
Striated Muscles ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Dihydropyridine Receptors ◽  
Long Range Interactions ◽  
Cardiac Muscles

The ryanodine receptor (RyR) is a high-conductance Ca2+ channel of the sarcoplasmic reticulum in muscle and of the endoplasmic reticulum in other cells. In striated muscle fibers, RyRs are responsible for the rapid release of Ca2+ that activates contraction. Ryanodine receptors are complex molecules, with unusually large cytoplasmic domains containing numerous binding sites for agents that control the state of activity of the channel-forming domain of the molecule. Structural considerations indicate that long-range interactions between cytoplasmic and intramembrane domains control channel function. Ryanodine receptors are located in specialized regions of the SR, where they are structurally and functionally associated with other intrinsic proteins and, indirectly, also with the luminal Ca2(+)-binding protein calsequestrin. Activation of RyRs during the early part of the excitation-contraction coupling cascade is initiated by the activity of surface-membrane Ca2+ channels, the dihydropyridine receptors (DHPRs). Skeletal and cardiac muscles contain different RyR and DHPR isoforms and both contribute to the diversity in cardiac and skeletal excitation-contraction coupling mechanisms. The architecture of the sarcoplasmic reticulum-surface junctions determines the types of RyR-DHPR interactions in the two muscle types.

scholarly journals Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

1998 ◽  
Vol 76 (5) ◽  
pp. 681-694 ◽  
Author(s):  
Peng Leong ◽  
David H MacLennan
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Dihydropyridine Receptor ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Receptor Proteins ◽  
Contraction Coupling ◽  
Experimental Systems ◽  
Complex Interactions

Evidence for functional interactions between the Ca2+ release channel in the skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) and the L-type Ca2+ channel in the sarcolemma (the dihydropyridine receptor), leading to excitation-contraction coupling, is reviewed and experimental systems used to identify candidate sites of interaction are outlined.Key words: sarcoplasmic reticulum, excitation-contraction coupling.

Ryanodine modifies conductance and gating behavior of single Ca2+ release channel

1987 ◽  
Vol 253 (3) ◽  
pp. C364-C368 ◽  
Author(s):  
E. Rousseau ◽  
J. S. Smith ◽  
G. Meissner
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Lipid Bilayers ◽  
Single Channel ◽  
Ruthenium Red ◽  
Planar Lipid Bilayers ◽  
Open Probability ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling

Ryanodine affects excitation-contraction coupling in skeletal and cardiac muscle by specifically interacting with the sarcoplasmic reticulum (SR) Ca2+ release channel. The effect of the drug at the single channel level was studied by incorporating skeletal and cardiac SR vesicles into planar lipid bilayers. The two channels were activated by micromolar free Ca2+ and millimolar ATP and inhibited by Mg2+ and ruthenium red. Addition of micromolar concentrations of ryanodine decreased about twofold the unit conductance of the Ca2+- and ATP-activated skeletal and cardiac channels. A second effect of ryanodine was to increase the open probability (Po) of the channels in such a way that Po was close to unity under a variety of activating and inactivating conditions. The effects of ryanodine were long lasting in that removal of ryanodine by perfusion did not return the channels into their fully conducting state.

scholarly journals Localization in the II-III Loop of the Dihydropyridine Receptor of a Sequence Critical for Excitation-Contraction Coupling

1998 ◽  
Vol 273 (39) ◽  
pp. 24983-24986 ◽  
Author(s):  
Junichi Nakai ◽  
Tsutomu Tanabe ◽  
Takashi Konno ◽  
Brett Adams ◽  
Kurt G. Beam
Keyword(s):  
Dihydropyridine Receptor ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling

Caffeine sensitivity of native RyR channels from normal and malignant hyperthermic pigs: effects of a DHPR II–III loop peptide

2004 ◽  
Vol 286 (4) ◽  
pp. C821-C830 ◽  
Author(s):  
Esther M. Gallant ◽  
James Hart ◽  
Kevin Eager ◽  
Suzanne Curtis ◽  
Angela F. Dulhunty
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Malignant Hyperthermia ◽  
Lipid Bilayers ◽  
Ryanodine Receptor ◽  
High Affinity ◽  
Enhanced Sensitivity ◽  
Skeletal Muscle Contraction ◽  
Activation Mechanisms ◽  
Standard Tests

Enhanced sensitivity to caffeine is part of the standard tests for susceptibility to malignant hyperthermia (MH) in humans and pigs. The caffeine sensitivity of skeletal muscle contraction and Ca2+ release from the sarcoplasmic reticulum is enhanced, but surprisingly, the caffeine sensitivity of purified porcine ryanodine receptor Ca2+-release channels (RyRs) is not affected by the MH mutation (Arg615Cys). In contrast, we show here that native malignant hyperthermic pig RyRs (incorporated into lipid bilayers with RyR-associated lipids and proteins) were activated by caffeine at 100- to 1,000-fold lower concentrations than native normal pig RyRs. In addition, the results show that the mutant ryanodine receptor channels were less sensitive to high-affinity activation by a peptide (CS) that corresponds to a part of the II–III loop of the skeletal dihydropyridine receptor (DHPR). Furthermore, subactivating concentrations of peptide CS enhanced the response of normal pig and rabbit RyRs to caffeine. In contrast, the caffeine sensitivity of MH RyRs was not enhanced by the peptide. These novel results showed that in MH-susceptible pig muscles 1) the caffeine sensitivity of native RyRs was enhanced, 2) the sensitivity of RyRs to a skeletal II–III loop peptide was depressed, and 3) an interaction between the caffeine and peptide CS activation mechanisms seen in normal RyRs was lost.

Calmodulin and Excitation-Contraction Coupling

Physiology ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 281-284 ◽  
Author(s):  
Susan L. Hamilton ◽  
Irina Serysheva ◽  
Gale M. Strasburg
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Sarcoplasmic Reticulum ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Transverse Tubule ◽  
Contraction Coupling ◽  
Voltage Dependent ◽  
Important Regulator ◽  
Precise Role

Excitation-contraction coupling in cardiac and skeletal muscle involves the transverse-tubule voltage-dependent Ca2+ channel and the sarcoplasmic reticulum Ca2+ release channel. Both of these ion channels bind and are modulated by calmodulin in both its Ca2+-bound and Ca2+-free forms. Calmodulin is, therefore, potentially an important regulator of excitation-contraction coupling. Its precise role, however, has not yet been defined.

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