Chloride-dependent sarcoplasmic reticulum Ca2+ release correlates with increased Ca2+ activation of ryanodine receptors

Fruen, Bradley R.; Kane, Patricia K.; Mickelson, James R.; Louis, Charles F.

doi:10.1016/s0006-3495(96)79445-6

Cited by 29 publications

(33 citation statements)

References 30 publications

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“…The ability of myoplasmic Cl -to potentiate Ca 2+ leakage from the SR was Ca 2+ dependent, as it was not observed when the [Ca 2+ ] was strongly buffered to a very low level (10 nM or pCa 8) (Table 1). This Ca 2+ dependent increase in Ca 2+ efflux is very similar to the effect reported by Fruen et al [10], where 150 mM Cl -increased the rate of Ca 2+ release from porcine SR vesicles in the presence of 3 µM Ca 2+ , but had little if any effect at 30 nM Ca 2+ . In the experiments here at pCa 6.7 (i.e.…”

Section: Discussionsupporting

confidence: 90%

“…However, more recent experiments have provided evidence that high myoplasmic [Cl -] directly enhances the activation of RyR-1 [10,24], supporting an earlier proposal of Hasselbach and Migala [12] that this is the mechanism by which Cl -induces Ca 2+ release (see also [5]). Interestingly, the effect was not present in the cardiac SR vesicles [10] and cardiac fibres do not show Cl --induced Ca 2+ release [7]. Furthermore, experiments with permeabilized skeletal muscle fibres from mutant newborn mice lacking RyR-1 showed that, under conditions where there should be little or no osmotic effects (K + -methanesulphonate replaced with choline chloride), Cl --induced Ca 2+ release was largely or completely absent [14], strongly indicating that such release is predominantly mediated by RyR-1.…”

Section: Introductionsupporting

confidence: 63%

“…It has also been proposed that Cl --induced Ca 2+ release is mediated by the movement of Ca 2+ and Cl -as a salt pair through a non-selective SR channel [37], and that this might then be reinforced by Ca 2+ efflux through the major mammalian skeletal muscle Ca 2+ release channel, the ryanodine receptor type 1 (RyR-1) [30]. However, more recent experiments have provided evidence that high myoplasmic [Cl -] directly enhances the activation of RyR-1 [10,24], supporting an earlier proposal of Hasselbach and Migala [12] that this is the mechanism by which Cl -induces Ca 2+ release (see also [5]). Interestingly, the effect was not present in the cardiac SR vesicles [10] and cardiac fibres do not show Cl --induced Ca 2+ release [7].…”

Section: Introductionmentioning

confidence: 99%

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Effect of chloride on Ca 2+ release from the sarcoplasmic reticulum of mechanically skinned skeletal muscle fibres

Coonan

Lamb

1998

Pfl�gers Archiv European Journal of Physiology

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The effect of intracellular Cl- on Ca2+ release in mechanically skinned fibres of rat extensor digitorum longus (EDL) and toad iliofibularis muscles was examined under physiological conditions of myoplasmic [Mg2+] and [ATP] and sarcoplasmic reticulum (SR) Ca2+ loading. Both in rat and toad fibres, the presence of 20 mM Cl- in the myoplasm increased Ca2+ leakage from the SR at pCa (i.e. -log10 [Ca2+]) 6.7, but not at pCa 8. Ca2+ uptake was not significantly affected by the presence of Cl-. This Ca2+-dependent effect of Cl- on Ca2+ leakage was most likely due to a direct action on the ryanodine receptor/Ca2+ release channel, and could influence channel sensitivity and the resting [Ca2+] in muscle fibres in vivo. In contrast to this effect, acute addition of 20 mM Cl- to the myoplasm caused a 40-50% reduction in Ca2+ release in response to a low caffeine concentration both in toad and rat fibres. One possible explanation for this latter effect is that the addition of Cl- induces a potential across the SR (lumen negative) which might reduce Ca2+ release via several different mechanisms.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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Effect of chloride on Ca 2+ release from the sarcoplasmic reticulum of mechanically skinned skeletal muscle fibres

Coonan

Lamb

1998

Pfl�gers Archiv European Journal of Physiology

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“…Thus the absolute magnitude of the increase in ryanodine binding (i.e., [ 3 H]ryanodine binding at a given perchlorate concentration over that in the absence of perchlorate) was not significantly different for normal and MHS SR vesicles [3.05 ± 0.31 pmol/mg and 2.52 ± 0.42 pmol/mg for normal and MHS SR respectively at 40 mM perchlorate (P > 0.05)]. Finally, as reported by Fruen et al [4,5], there was no indication of a maximum stimulation of ryanodine binding by perchlorate over the range of perchlorate concentrations examined in this study (Fig. 4, inset).…”

Section: Potentiation Of Twitch Tension By Perchloratesupporting

confidence: 68%

The action of perchlorate on malignant-hyperthermia-susceptible muscle

Anderson

Fruen

Jordan

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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To better understand the altered skeletal muscle excitation-contraction (E-C) coupling that occurs in malignant hyperthermia, we have examined the potentiating actions of perchlorate in intact muscle fiber bundles, isolated sarcoplasmic reticulum (SR) vesicles, and the purified ryanodine receptor/Ca2+ release channel (RyR) isolated from malignant-hyperthermia-susceptible (MHS) and normal porcine muscle. The concentration of perchlorate that half-maximally potentiated twitch tension (2.5-3.5 mM) was not significantly different for MHS and normal muscles. The effect of perchlorate on fractional twitch force was significantly greater for normal than for MHS muscle, although the absolute twitch potentiation was similar for both muscle types. The K-contracture threshold of MHS muscle bundles is significantly lower than that of normal bundles; perchlorate shifted the K-contraction activation curves of both MHS and normal muscle bundles to lower K+ concentrations. Perchlorate both increased ryanodine binding to MHS and normal SR vesicles and increased single-channel open probability of the purified MHS and normal RyR. In both cases, the percentage increase was greater for normal than for MHS preparations; however, the absolute increase in activity was not different for MHS and normal RyR indicating that there is no difference in the perchlorate sensitivity of MHS and normal SR Ca2+ release channels. Thus, the greater absolute responses of the MHS Ca2+ release channel in the presence of perchlorate is likely to be due to the greater basal activity of the MHS release channel and does not reflect an underlying defect in the site of action of perchlorate on the MHS skeletal muscle Ca2+ release channel.

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“…Previous work from our laboratory has suggested that, whereas RYR1 channels exhibit changeable Ca 2ϩ activation properties, cardiac RYR2 channels appear to exhibit a more consistent Ca 2ϩ -activable state (43). In terms of the present model (Fig.…”

Section: Dantrolene May Act Directly At Ryr1 Channels To Limit Activamentioning

confidence: 54%

Dantrolene Inhibition of Sarcoplasmic Reticulum Ca2+Release by Direct and Specific Action at Skeletal Muscle Ryanodine Receptors

Fruen

Mickelson

Louis

1997

Journal of Biological Chemistry

196

169

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The skeletal muscle relaxant dantrolene inhibits the release of Ca 2؉ from the sarcoplasmic reticulum during excitation-contraction coupling and suppresses the uncontrolled Ca 2؉ release that underlies the skeletal muscle pharmacogenetic disorder malignant hyperthermia; however, the molecular mechanism by which dantrolene selectively affects skeletal muscle Ca 2؉ regulation remains to be defined. Here we provide evidence of a high-affinity, monophasic inhibition by dantrolene of ryanodine receptor Ca 2؉ channel function in isolated sarcoplasmic reticulum vesicles prepared from malignant hyperthermia-susceptible and normal pig skeletal muscle. In media simulating resting myoplasm, dantrolene increased the half-time for 45 Ca 2؉ release from both malignant hyperthermia and normal vesicles approximately 3. The muscle relaxant dantrolene is a potent and specific inhibitor of skeletal muscle excitation-contraction (E-C) 1 coupling (1). Dantrolene (ϳ10 M) reduces skeletal muscle twitch force by approximately 75% (2) and shifts the sensitivity of contractile activation to higher voltages (3, 4), these effects being attributed to a partial block by dantrolene of Ca 2ϩ release from the sarcoplasmic reticulum (SR) (1,5,6). In contrast to these pronounced effects on skeletal muscle, effects of dantrolene on cardiac muscle contractility are mild or absent (1, 5, 7). Clinically, dantrolene has proven effective in the treatment of malignant hyperthermia (MH), a potentially fatal genetic disorder of skeletal muscle E-C coupling in which exposure to volatile anesthetics triggers uncontrolled SR Ca 2ϩ release, muscle contracture, and accelerated metabolism (8).The molecular basis of the action of dantrolene remains undefined but is generally presumed to involve either direct or indirect inhibitory effects on ryanodine receptor (RYR) Ca 2ϩ channels. To date, three RYR isoforms have been identified in mammalian tissues and are termed RYR1, RYR2, and RYR3 (9). In skeletal muscle, the RYR1 isoform is the major pathway for SR Ca 2ϩ release during E-C coupling, and defects in these channels have been linked to MH susceptibility in pigs and in certain human families (8, 10). Moreover, recent evidence indicates that high-affinity [3 H]dantrolene and [ 3 H]ryanodine binding sites are localized to the same or closely associated skeletal muscle SR membrane fractions (11, 12). RYR1 channels thus constitute a likely target for the physiologic and therapeutic actions of dantrolene on skeletal muscle Ca 2ϩ regulation. Nonetheless, the precise mechanism by which dantrolene may affect the activation of RYR1 channels has remained unclear. In particular, it is not yet clear how dantrolene may alter RYR1 activation by the physiologic effectors of these channels that have been identified in studies using isolated SR vesicles preparations (13). In addition, whether the effects of dantrolene may reflect a direct interaction with the RYR1 channel complex itself or rather require dantrolene binding to a separate and as yet unidentified regulatory molecu...

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Chloride-dependent sarcoplasmic reticulum Ca2+ release correlates with increased Ca2+ activation of ryanodine receptors

Cited by 29 publications

References 30 publications

Effect of chloride on Ca 2+ release from the sarcoplasmic reticulum of mechanically skinned skeletal muscle fibres

Effect of chloride on Ca 2+ release from the sarcoplasmic reticulum of mechanically skinned skeletal muscle fibres

The action of perchlorate on malignant-hyperthermia-susceptible muscle

Dantrolene Inhibition of Sarcoplasmic Reticulum Ca2+Release by Direct and Specific Action at Skeletal Muscle Ryanodine Receptors

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