4-chloro-orto-cresol activates ryanodine receptor more selectively and potently than 4-chloro-meta-cresol

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4-Chloro-m-cresol, a potent and specific activator of the skeletal muscle ryanodine receptor.

The aim of the present study was to determine the effects of 4-chloro-m-cresol (4-CmC), a preservative often added to drugs intravenously administered, on the skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor. In heavy SR vesicles obtained from rabbit back muscles, 4-CmC stimulated (Ca2+)-activated [3H]ryanodine binding with an EC50 of about 100 microM. In the ...

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Structural determinants of 4-chloro-m-cresol required for activation of ryanodine receptor type 1.

4-Chloro-m-cresol (4-CmC) is a clinically relevant activator of the intracellular Ca2+ release channel, the ryanodine receptor isoform 1 (RyR1). In this study, the chemical moieties on the 4-CmC molecule required for its activation of RyR1 were determined using structure-activity relationship analysis with a set of commercially available 4-CmC analogs. Separate compounds each lacking one of the...

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Commonly used ryanodine receptor activator, 4-chloro-m-cresol (4CmC), is also an inhibitor of SERCA Ca2+ pumps.

4-Chloro-m-cresol (4CmC) is an extensively used activator of ryanodine receptors (RyRs). Studies have shown that 4CmC, at a concentration of 1 mM, is sufficient to cause Ca(2+) release through RyRs. Here, we show that mM concentrations of 4CmC also inhibit the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA), (IC(50) 2-3mM) and cause Ca(2+) release. 4CmC also causes increased intracellu...

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4-Chloro-m-cresol: a specific tool to distinguish between malignant hyperthermia-susceptible and normal muscle.

Single-channel recordings have indicated that ryanodine receptor (RyR1) mutation Arg615Cys of porcine malignant hyperthermia-susceptible (MHS) muscle is not directly associated with the enhanced caffeine sensitivity of MH(S) muscle [1]. In the present study, the effect of a novel activator of RyR1, 4-chlorom-cresol (4-CmC), was investigated on high-affinity [3H]ryanodine binding to porcine skel...

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Voltage-dependent block of normal and mutant muscle sodium channels by 4-Chloro-m-Cresol.

1 The effects of 4-Chloro-m-Cresol (4-CmC) were examined on heterologously expressed wild type (WT), Paramyotonia Congenita (R1448H) and Hyperkalemic Periodic Paralysis (M1360V) mutant alpha-subunits of human muscle sodium channels. 2 Block of rested sodium channels caused by 4-CmC was concentration-dependent with an ECR50 of 0.40 mM in WT, 0.45 mM in R1448H and 0.49 mM in M1360V. 3 Inactivatio...

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ژورنال

عنوان ژورنال: Cell Calcium

سال: 2020

ISSN: 0143-4160

DOI: 10.1016/j.ceca.2020.102213