scholarly journals The N-Terminal Region of the Ryanodine Receptor Affects Channel Activation

2017 ◽  
Vol 8 ◽  
Author(s):  
Andrea Faltinova ◽  
Nataša Tomaskova ◽  
Marián Antalik ◽  
Jozef Sevcik ◽  
Alexandra Zahradnikova
Keyword(s):  
Ryanodine Receptor ◽  
Terminal Region ◽  
Channel Activation

Human Cardiac Ryanodine Receptor: Preparation, Crystallization and Preliminary X-ray Analysis of the N-terminal Region

2013 ◽  
Vol 20 (11) ◽  
pp. 1211-1216 ◽  
Author(s):  
L’ubomír Borko ◽  
Július Kostan ◽  
Alexandra Zahradníkova ◽  
Vladimír Pevala ◽  
Juraj Gasperík ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Terminal Region ◽  
X Ray ◽  
Cardiac Ryanodine Receptor

scholarly journals Divergent Activity Profiles of Type 1 Ryanodine Receptor Channels Carrying Malignant Hyperthermia and Central Core Disease Mutations in the Amino-Terminal Region

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130606 ◽  
Author(s):  
Takashi Murayama ◽  
Nagomi Kurebayashi ◽  
Toshiko Yamazawa ◽  
Hideto Oyamada ◽  
Junji Suzuki ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Terminal Region ◽  
Central Core ◽  
Central Core Disease ◽  
Amino Terminal ◽  
Disease Mutations

Spontaneous Ryanodine-Receptor-Dependent Ca2+-Activated K+ Currents and Hyperpolarizations in Rat Medial Preoptic Neurons

2010 ◽  
Vol 103 (5) ◽  
pp. 2900-2911 ◽  
Author(s):  
Göran Klement ◽  
Michael Druzin ◽  
David Haage ◽  
Evgenya Malinina ◽  
Peter Århem ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Ryanodine Receptors ◽  
Underlying Mechanism ◽  
Sk Channels ◽  
Patch Clamp Technique ◽  
Channel Activation ◽  
Impulse Generation ◽  
Outward Currents ◽  
Main Charge ◽  
Perforated Patch Clamp

The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of ∼0.5 Hz and with a decay time constant of ∼200 ms, were frequently detected in neurons when voltage-clamped between approximately −70 and −30 mV. The dependence on extracellular K+ concentration was consistent with K+ as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca2+-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca2+ release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > −30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca2+ release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.

scholarly journals The Predicted TM10 Transmembrane Sequence of the Cardiac Ca2+Release Channel (Ryanodine Receptor) Is Crucial for Channel Activation and Gating

2003 ◽  
Vol 279 (5) ◽  
pp. 3635-3642 ◽  
Author(s):  
Ruiwu Wang ◽  
Jeff Bolstad ◽  
Huihui Kong ◽  
Lin Zhang ◽  
Cindy Brown ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Release Channel ◽  
Channel Activation ◽  
Transmembrane Sequence

Interaction of the Lys3614–Asn3643 calmodulin-binding domain with the Cys4114-Asn4142 region of the type 1 ryanodine receptor is involved in the mechanism of Ca2+/agonist-induced channel activation

2008 ◽  
Vol 411 (2) ◽  
pp. 415-423 ◽  
Author(s):  
Jaya P. Gangopadhyay ◽  
Noriaki Ikemoto
Keyword(s):  
Ryanodine Receptor ◽  
Binding Activity ◽  
Significant Inhibition ◽  
Binding Domain ◽  
Domain Pair ◽  
Dependent Manner ◽  
Domain Interaction ◽  
Channel Activation ◽  
Calmodulin Binding

In the present study we show that the interaction of the CaM (calmodulin)-binding domain (Lys3614–Asn3643) with the Cys4114–Asn4142 region (a region included in the CaM-like domain) serves as an intrinsic regulator of the RyR1 (type-1 ryanodine receptor). We tested the effects of antibodies raised against the two putative key regions of RyR1 [anti-(Lys3614–Asn3643) and anti-(Cys4114–Asn4142) antibodies]. Both antibodies produced significant inhibition of [3H]ryanodine-binding activity of RyR1. This suggests that the inter-domain interaction between the two domains, Lys3614–Asn3643 and Cys4114–Asn4142, activates the channel, and that the binding of antibody to either side of the interacting domain pair interfered with the formation of a ‘channel-activation link’ between the two regions. In order to spectroscopically monitor the mode of interaction of these domains, the site of inter-domain interaction was fluorescently labelled with MCA [(7-methoxycoumarin-4-yl)acetyl] in a site-directed manner. The accessibility of the bound MCA to a large molecular mass fluorescence quencher, BSA-QSY (namely, the size of a gap between the interacting domains) decreased with an increase of [Ca2+] in a range of 0.03–2.0 μM, as determined by Stern–Volmer fluorescence quenching analysis. The Ca2+-dependent decrease in the quencher accessibility was more pronounced in the presence of 150 μM 4-CmC (4-chlorometacresol), and was reversed by 1 mM Mg2+ (a well-known inhibitor of Ca2+/agonist-induced channel activation). These results suggest that the Lys3614–Asn3643 and Cys4114–Asn4142 regions of RyR1 interact with each other in a Ca2+- and agonist-dependent manner, and this serves as a mechanism of Ca2+- and agonist-dependent activation of the RyR1 Ca2+ channel.

scholarly journals Molecular Basis of Ca2+ Binding to the Ryanodine Receptor for Channel Activation

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO2-3-49
Author(s):  
Takashi Murayama ◽  
Haruo Ogawa ◽  
Nagomi Kurebayashi ◽  
Seiko Ohno ◽  
Minoru Horie ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Molecular Basis ◽  
Channel Activation

scholarly journals Cardiac ryanodine receptor N-terminal region biosensors identify novel inhibitors via FRET-based high-throughput screening

2021 ◽  
pp. 101412
Author(s):  
Jingyan Zhang ◽  
Daniel P. Singh ◽  
Christopher Y. Ko ◽  
Roman Nikolaienko ◽  
Siobhan M. Wong King Yuen ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
High Throughput ◽  
High Throughput Screening ◽  
Terminal Region ◽  
Cardiac Ryanodine Receptor

A brain-specific transcript from the 3′-terminal region of the skeletal muscle ryanodine receptor gene

FEBS Letters ◽  
1993 ◽  
Vol 322 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Hiroshi Takeshima ◽  
Seiichiro Nishimura ◽  
Miyuki Nishi ◽  
Michiko Ikeda ◽  
Tetsuo Sugimoto
Keyword(s):  
Skeletal Muscle ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Terminal Region ◽  
Specific Transcript

scholarly journals Antibody probe study of Ca2+ channel regulation by interdomain interaction within the ryanodine receptor

2004 ◽  
Vol 380 (2) ◽  
pp. 561-569 ◽  
Author(s):  
Shigeki KOBAYASHI ◽  
Takeshi YAMAMOTO ◽  
Jerome PARNESS ◽  
Noriaki IKEMOTO
Keyword(s):  
Ryanodine Receptor ◽  
Fluorescence Probe ◽  
Aqueous Environment ◽  
Channel Activation ◽  
Regulatory Domains ◽  
Domain Specific ◽  
Terminal Domain ◽  
Domain Interactions ◽  
Interdomain Interaction ◽  
Domain Peptide

N-terminal and central domains of ryanodine receptor 1 (RyR1), where many reported malignant hyperthermia (MH) mutations are localized, represent putative channel regulatory domains. Recent domain peptide (DP) probe studies led us to the hypothesis that these domains interact to stabilize the closed state of channel (zipping), while weakening of domain–domain interactions (unzipping) by mutation de-stabilizes the channel, making it leaky to Ca2+ or sensitive to the agonists of RyR1. As shown previously, DP1 (N-terminal domain peptide) and DP4 (central domain peptide) produced MH-like channel activation/sensitization effects, presumably by peptide binding to sites critical to stabilizing domain–domain interactions and resultant loss of conformational constraints. Here we report that polyclonal anti-DP1 and anti-DP4 antibodies also produce MH-like channel activation and sensitization effects as evidenced by about 4-fold enhancement of high affinity [3H]ryanodine binding to RyR1 and by a significant left-shift of the concentration-dependence of activation of sarcoplasmic reticulum Ca2+ release by polylysine. Fluorescence quenching experiments demonstrate that the accessibility of a DP4-directed, conformationally sensitive fluorescence probe linked to the RyR1 N-terminal domain is increased in the presence of domain-specific antibodies, consistent with the view that these antibodies produce unzipping of interacting domains that are of hindered accessibility to the surrounding aqueous environment. Our results suggest that domain-specific antibody binding induces a conformational change resulting in channel activation, and are consistent with the hypothesis that interacting N-terminal and central domains are intimately involved in the regulation of RyR1 channel function.

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