Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle

Laver, Derek R.; Rodén, Lennart; Ahern, Gerard P.; Eager, K. R.; Junankar, Pauline R.; Dulhunty, Angela F.

doi:10.1007/bf00235394

Cited by 161 publications

(251 citation statements)

References 54 publications

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“…Using the imaging technique to directly measure SR Ca 2ϩ release fluxes, in conjunction with the r = −0.44 P < 0.001 unique agonist, FPL64176, to manipulate the gating properties of L-type Ca 2ϩ channels, we have provided compelling evidence that SR Ca 2ϩ release during excitation-contraction coupling is terminated mainly by a local inactivation of RyRs in intact myocytes, whereas stochastic attrition, depletion of SR Ca 2ϩ , and the adaptation of RyRs observed in lipid-layers (20,21) do not participate or only play a contributing role in terminating Ca 2ϩ release in situ. This inactivation of RyRs may depend on the high local [Ca 2ϩ ]consequential to their own Ca 2ϩ release, as suggested previously in skinned fibers (2,18), SR vesicles (44), and in single RyRs in lipid bilayers (45)(46)(47), as well as recently in intact myocytes (48), showing that the rate of Ca 2ϩ spark termination is related to the magnitude of release flux. However, the possibility that the process is obligated to the activation of RyRs per se (49) cannot be excluded.…”

Section: ؉supporting

confidence: 68%

Termination of Ca ²⁺ release by a local inactivation of ryanodine receptors in cardiac myocytes

Sham

Song

Chen

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

157

151

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Section: ؉supporting

confidence: 68%

Termination of Ca ²⁺ release by a local inactivation of ryanodine receptors in cardiac myocytes

Sham

Song

Chen

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

157

151

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“…Ca 2+ activation of the lobster RyR therefore requires higher [Ca 2+ ] than any other isoform of RyR studied at the single channel level (Smith et al, 1986;Ashley & Williams, 1990;Bull & Marengo, 1993;Percival et al, 1994;Copello et al, 1997;Chen et al, 1997). The single channel studies demonstrate that inactivation of the lobster RyR by Ca 2+ occurs at only slightly higher levels than are generally required for inactivation of mammalian skeletal channels (Chu et al, 1993;Laver et al, 1995;Copello et al, 1997) but at lower levels to those required for inactivation of the mammalian cardiac RyR (Chu et al, 1993;Laver et al, 1995;Copello et al, 1997).…”

Section: Discussionmentioning

confidence: 90%

Evidence for novel caffeine and Ca²⁺ binding sites on the lobster skeletal ryanodine receptor

Zhang¹,

Williams²,

Sitsapesan³

1999

British J Pharmacology

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1 The e ects of Ca 2+ , ATP and ca eine on the gating of lobster skeletal muscle ryanodine receptors (RyR) was investigated after reconstitution of the channels into planar phospholipid bilayers and by using [ 3 H]-ryanodine binding studies. 2 The single channel studies reveal that the EC 50 (60 mM) for activation of the lobster skeletal RyR by Ca 2+ as the sole ligand is higher than for any other isoform of RyR studied. 3 Inactivation of the channel by Ca 2+ (EC 50 =1 mM) occurs at concentrations slightly higher than those required to inactivate mammalian skeletal RyR (RyR1) but lower than those required to inactivate mammalian cardiac RyR (RyR2). 4 Lifetime analysis demonstrates that cytosolic Ca 2+ , as the sole activating ligand, cannot fully open the lobster skeletal RyR (maximum Po approximately 0.2). The mechanism for the increase in open probability (Po) is an increase in both the frequency and the duration of the open events. 5 ATP is a very e ective activator of the lobster RyR and can almost fully open the channel in the presence of activating cytosolic [Ca 2+ ]. In the presence of 700 mM Ca 2+ , 1 mM ATP increased Po to approximately 0.8. 6 Ca eine, often used as a tool to identify the presence of RyR channels, is relatively ine ective and cannot increase Po above the level that can be attained with Ca 2+ alone. 7 The results reveal that ca eine increases Po by a di erent mechanism to that of cytosolic Ca 2+ demonstrating that the mechanism for channel activation by ca eine is not`sensitization' to cytosolic Ca 2+ . 8 By studying the mechanisms involved in the activation of the lobster RyR we have demonstrated that the channel responds in a unique manner to Ca 2+ and to ca eine. The results strongly indicate that these ligand binding sites on the channel are di erent to those on mammalian isoforms of RyR.

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“…bit skeletal channels [27] and native frog skeletal muscle [18]. Cooperative inhibition is also present in rabbit skeletal muscle channels [25].…”

Section: Resultsmentioning

confidence: 99%

Calcium dependence of ryanodine‐sensitive calcium channels from brain cortex endoplasmic reticulum

1996

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Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle

Cited by 161 publications

References 54 publications

Termination of Ca ²⁺ release by a local inactivation of ryanodine receptors in cardiac myocytes

Termination of Ca ²⁺ release by a local inactivation of ryanodine receptors in cardiac myocytes

Evidence for novel caffeine and Ca²⁺ binding sites on the lobster skeletal ryanodine receptor

Calcium dependence of ryanodine‐sensitive calcium channels from brain cortex endoplasmic reticulum

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Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle

Cited by 161 publications

References 54 publications

Termination of Ca 2+ release by a local inactivation of ryanodine receptors in cardiac myocytes

Termination of Ca 2+ release by a local inactivation of ryanodine receptors in cardiac myocytes

Evidence for novel caffeine and Ca2+ binding sites on the lobster skeletal ryanodine receptor

Calcium dependence of ryanodine‐sensitive calcium channels from brain cortex endoplasmic reticulum

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Termination of Ca ²⁺ release by a local inactivation of ryanodine receptors in cardiac myocytes

Termination of Ca ²⁺ release by a local inactivation of ryanodine receptors in cardiac myocytes

Evidence for novel caffeine and Ca²⁺ binding sites on the lobster skeletal ryanodine receptor