Calcium-sensitivity of the SR calcium release channel in failing and nonfailing human myocardium

1999 ◽  
Vol 94 (3) ◽  
pp. 145-151 ◽  
Author(s):  
U. Schotten ◽  
C. Schumacher ◽  
V. Conrads ◽  
V. Braun ◽  
F. Schöndube ◽  
...  
Keyword(s):  
Calcium Release ◽  
Calcium Sensitivity ◽  
Human Myocardium ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Sr Calcium Release

scholarly journals Modulation of the Frequency of Spontaneous Sarcoplasmic Reticulum Ca2+ Release Events (Ca2+ Sparks) by Myoplasmic [Mg2+] in Frog Skeletal Muscle

1998 ◽  
Vol 111 (2) ◽  
pp. 207-224 ◽  
Author(s):  
Alain Lacampagne ◽  
Michael G. Klein ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Frog Skeletal Muscle ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Event Frequency ◽  
Open Time ◽  
Channel Opening ◽  
Sr Calcium Release

The modulation by internal free [Mg2+] of spontaneous calcium release events (Ca2+ “sparks”) from the sarcoplasmic reticulum (SR) was studied in depolarized notched frog skeletal muscle fibers using a laser scanning confocal microscope in line-scan mode (x vs. t). Over the range of [Mg2+] from 0.13 to 1.86 mM, decreasing the [Mg2+] induced an increase in the frequency of calcium release events in proportion to [Mg2+]−1.6. The change of event frequency was not due to changes in [Mg-ATP] or [ATP]. Analysis of individual SR calcium release event properties showed that the variation in event frequency induced by the change of [Mg2+] was not accompanied by any changes in the spatiotemporal spread (i.e., spatial half width or temporal half duration) of Ca2+ sparks. The increase in event frequency also had no effect on the distribution of event amplitudes. Finally, the rise time of calcium sparks was independent of the [Mg2+], indicating that the open time of the SR channel or channels underlying spontaneous calcium release events was not altered by [Mg2+] over the range tested. These results suggest that in resting skeletal fibers, [Mg2+] modulates the SR calcium release channel opening frequency by modifying the average closed time of the channel without altering the open time. A kinetic reaction scheme consistent with our results and those of bilayer and SR vesicle experiments indicates that physiological levels of resting Mg2+ may inhibit channel opening by occupying the site for calcium activation of the SR calcium release channel.

Effects of the halothane-sensitivity gene on sarcoplasmic reticulum function

1989 ◽  
Vol 257 (4) ◽  
pp. C787-C794 ◽  
Author(s):  
J. R. Mickelson ◽  
E. M. Gallant ◽  
W. E. Rempel ◽  
K. M. Johnson ◽  
L. A. Litterer ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Protein Product ◽  
Receptor Protein ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Sr Calcium Release ◽  
Sensitivity Gene

Pigs heterozygous for the halothane-sensitivity gene exhibit a distinct phenotype with regard to both in vivo and in vitro muscle responses to halothane (E. M. Gallant, J. R. Mickelson, B. D. Roggow, S. K. Donaldson, C. F. Louis, and W. E. Rempel. Am. J. Physiol. 257 (Cell Physiol. 26): C781-C786, 1989). In this paper heavy sarcoplasmic reticulum (SR) preparations were isolated from the muscles of pigs of all three genotypes. The rate of calcium release from SR of pigs homozygous for the halothane-sensitivity gene was approximately twice that of SR from pigs homozygous for the normal allele. Furthermore, in the presence of 6 microM Ca2+, the binding of [3H]ryanodine to SR isolated from the homozygous halothane-sensitive pigs was of a higher affinity than was the binding to SR isolated from the homozygous normal pigs (Kd = 70-90 vs. 265 nM, respectively). The SR from pigs heterozygous for the halothane-sensitivity gene, however, demonstrated intermediate values for the rate of calcium release and the affinity for [3H]ryanodine (Kd = 192 nM). Thus the alterations in heavy SR calcium release and [3H]ryanodine binding in the pigs containing one copy of the halothane-sensitivity gene demonstrate a distinct heterozygote phenotype. These data also suggest that the protein product of this gene is closely associated with, and perhaps identical to, the SR calcium release channel-ryanodine receptor protein.

Inositol 1,4,5-trisphosphate releases intracellular Ca2+ in permeabilized chick atria

1990 ◽  
Vol 258 (6) ◽  
pp. H1745-H1752 ◽  
Author(s):  
A. M. Vites ◽  
A. Pappano
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Induced Response ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Loading Cycle ◽  
Maximum Tension ◽  
Atrial Muscle ◽  
Inositol 1,4,5 Trisphosphate ◽  
Sr Calcium Release

Inositol 1,4,5-trisphosphate (IP3) and caffeine evoked transient, reversible, and concentration-dependent increases in tension in saponin-treated chick atrial muscle. Contractures evoked by IP3 and caffeine were detected in solutions with 70 microM EGTA at pCa 7.0. In the presence of 7 mM EGTA, neither IP3 nor caffeine was able to evoke a contracture. Maximally effective concentrations of IP3 (20 microM) and caffeine (20 mM) developed tensions to approximately 44 and 83% of that elicited by pCa 5.0 (maximum tension = 100%), respectively. The IP3- or caffeine-induced contractures were consistently reproduced when the sarcoplasmic reticulum (SR) had previously been loaded with calcium. Preexposure to caffeine suppressed the following IP3-induced response. When ryanodine (1-10 microM) was present throughout the SR-loading cycle, the responses to IP3 and caffeine were prevented. However, when ryanodine was added after the SR was loaded with calcium, neither the response to IP3 nor that to caffeine was affected. These results are consistent with the hypothesis that ryanodine inhibition requires prior activation of the SR calcium-release channel. It is concluded that both IP3 and caffeine increased tension in the SR by releasing calcium from it. The effect of IP3 is consistent with its messenger role as a calcium-mobilizing agent.

scholarly journals Unravelling calcium-release channel gating: clues from a hot disease

2004 ◽  
Vol 380 (1) ◽  
pp. e1-e3 ◽  
Author(s):  
Tommie V. McCARTHY ◽  
John J. MACKRILL
Keyword(s):  
Calcium Release ◽  
Distinct Point ◽  
Ryanodine Receptors ◽  
Point Mutations ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Present Evidence ◽  
Gating Mechanism ◽  
Biochemical Journal ◽  
Interdomain Interactions

Ryanodine receptors (RyRs) are a family of intracellular channels that mediate Ca2+ release from the endoplasmic and sarcoplasmic reticulum. More than 50 distinct point mutations in one member of this family, RyR1, cause malignant hyperthermia, a potentially lethal pharmacogenetic disorder of skeletal muscle. These mutations are not randomly distributed throughout the primary structure of RyR1, but are grouped in three discrete clusters. In this issue of the Biochemical Journal, Kobayashi et al. present evidence that interdomain interactions between two of these mutation-enriched regions play a key role in the gating mechanism of RyR1.

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