Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

Nakai, Junichi; Dirksen, Robert T.; Nguyen, Hanh T.; Pessah, Isaac N.; Beam, Kurt G.; Allen, Paul D.

doi:10.1038/380072a0

Cited by 445 publications

(489 citation statements)

References 29 publications

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“…Such a signal is termed retrograde signalling [10]. Chavis et al have shown a similar signal in cerebellar granule cells [12], where RyRs activated by type-1 metabotropic glutamate receptors increase VACC activity.…”

Section: Discussionmentioning

confidence: 97%

“…The cardiac and brain isoforms of type-2 RyRs (RyR-2) and brain isoforms of type-3 RyRs (RyR-3) [5,6] are activated by cADPR [7,8], but the skeletal-muscle isoforms of type-1 RyRs (RyR-1) are not [8,9]. Whereas RyR-1 is coupled to L-type voltage-activated Ca# + channels (VACCs) through proteinprotein interactions [10], such direct coupling has not been shown in RyR-2 and RyR-3. In neurons, instead, a link from Ntype VACCs to RyRs (an orthograde influence) [11] and a functional coupling from RyRs to L-type VACCs (a retrograde signal) [12] have been reported.…”

Section: Introductionmentioning

confidence: 99%

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cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells

Hashii

Minabe

Higashida

2000

Biochemical Journal

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The effects of cADP-ribose (cADPR), a metabolite of β-NAD + , on the elevation of cytoplasmic free Ca# + concentration ([Ca# + ] i ) and Ca# + influx through voltage-activated Ca# + channels (VACCs) were studied in NG108-15 neuroblastomaiglioma hybrid cells. NG108-15 cells were pre-loaded with fura-2 and whole-cell patch-clamped. Application of cADPR through patch pipettes did not by itself trigger any [Ca# + ] i rise at the resting membrane potential. A rise in [Ca# + ] i was evoked upon sustained membrane depolarization, and was significantly larger in cADPR-infused cells than in non-infused cells. This potentiation in the [Ca# + ] i elevation was reproduced by infusion of β-NAD + , and was blocked by 8-bromo-cADPR and antagonized by external application of ryanodine or by pretreatment of cells with FK506. Nicotinamide inhibited β-NAD + -induced, but not cADPR-elicited, potentiation. [Ca# + ] i increases or Ca# + influx,

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells

Hashii

Minabe

Higashida

2000

Biochemical Journal

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“…Our results support the hypothesis of a retrograde communication between the SR Ca 2+ release channel and the L-type Ca 2+ channel (DHPR). This communication may be mediated in some cases by a direct interaction between the two channel proteins, L-type Ca 2+ channel and RyR 2 [33]. Effects of siRNA3 target on mRNA and protein levels of RyR 2 in rat primary cardiomyocytes with transfection after 6-72 h tested by RT-PCR and western blot.…”

Section: Discussionmentioning

confidence: 99%

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

Fu¹,

Li²,

Fan³

et al. 2008

Biochemical Pharmacology

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The present study established a model of RyR 2 knockdown cardiomyocytes and elucidated the role of RyR 2 in aconitine-induced arrhythmia. Cardiomyocytes were obtained from hearts of neonatal Sprague-Dawlay rats. siRNAs were used to down-regulate RyR 2 expression. Reduction of RyR 2 expression was documented by RT-PCR, western blot, and immunofluorescence. Ca 2+ signals were investigated by measuring the relative intracellular Ca 2+ concentration, spontaneous Ca 2+ oscillations, caffeine-induced Ca 2+ release, and L-type Ca 2+ currents. In normal cardiomyocytes, steady and periodic spontaneous Ca 2+ oscillations were observed, and the baseline [Ca 2+ ] i remained at the low level. Exposure to 3 μM aconitine increased the frequency and decreased the amplitude of Ca 2+ oscillations; the baseline [Ca 2+ ] i and the level of caffeineinduced Ca 2+ release were increased but the L-type Ca 2+ currents were inhibited after application of 3 μM aconitine for 5 min. In RyR 2 knockdown cardiomyocytes, the steady and periodic spontaneous Ca 2+ oscillations almost disappeared, but were re-induced by aconitine without affecting the baseline [Ca 2+ ] i level; the level of caffeine-induced Ca 2+ release was increased but L-type Ca 2+ currents were inhibited. Alterations of RyR 2 are important consequences of aconitinestimulation and activation of RyR 2 appear to have a direct relationship with aconitine-induced arrhythmias. The present study demonstrates a potential method for preventing aconitine-induced arrhythmias by inhibiting Ca 2+ leakage through the sarcoplasmic reticulum RyR 2 channel.

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“…They found faster activation and inactivation kinetics of DHPRs incorporated in lipid bilayers when purified RyR1 was added to the cis-chamber. However, the term "retrograde signaling" was coined several years later when DHPR-RyR interactions were investigated by electrophysiological characterization of dyspedic skeletal muscle myotubes (Nakai et al 1996). Dyspedic myotubes have a homozygous mutation of the RyR1 gene and do not express functional RyR Ca 2+ release channels.…”

Section: Retrograde Ryr-dhpr Couplingmentioning

confidence: 99%

New factors contributing to dynamic calcium regulation in the skeletal muscle triad—a crowded place

2009

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Skeletal muscle is a highly organized tissue that has to be optimized for fast signalling events conveying electrical excitation to contractile response. The site of electro-chemico-mechanical coupling is the skeletal muscle triad where two membrane systems, the extracellular ttubules and the intracellular sarcoplasmic reticulum, come into very close contact. Structure fits function here and the signalling proteins DHPR and RyR1 were the first to be discovered to bridge this gap in a conformational coupling arrangement. Since then, however, new proteins and more signalling cascades have been identified just in the last decade, adding more diversity and fine tuning to the regulation of excitation-contraction coupling (ECC) and control over Ca 2+ store content. The concept of Ca 2+ entry into working skeletal muscle has become attractive again with the experimental evidence summarized in this review. Store-operated Ca 2+ entry (SOCE), excitation-coupled Ca 2+ entry (ECCE), action-potential-activated Ca 2+ current (APACC), and retrograde EC-coupling (ECC) are new concepts additional to the conventional orthograde ECC; they have provided fascinating new insights into muscle physiology. In this review, we discuss the discovery of these pathways, their potential roles, and the signalling proteins involved that show that the triad may become a crowded place in time.

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Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

Cited by 445 publications

References 29 publications

cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells

cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

New factors contributing to dynamic calcium regulation in the skeletal muscle triad—a crowded place

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