School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK B15 2TT, United Kingdom.
Pharmacol Rep. 2009 Sep-Oct;61(5):838-42. doi: 10.1016/s1734-1140(09)70139-2.
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 intracellular [Ca(2+)] levels in COS-7 cells, which lack functional RyRs. Thus, any increase in [Ca(2+)] levels associated with use of 4CmC (>or= 1mM) could lead to non-specific Ca(2+) changes due to SERCA inhibition rather than RyR activation.
4-氯间甲酚（4CmC）是一种广泛使用的肌浆网钙释放通道（RyR）激活剂。研究表明，1mM 的 4CmC 浓度足以通过 RyR 引起 Ca2+释放。在这里，我们发现 mM 浓度的 4CmC 也抑制肌浆网内质网 Ca2+-ATP 酶（SERCA）（IC50 为 2-3mM）并导致 Ca2+释放。4CmC 还导致缺乏功能性 RyR 的 COS-7 细胞内 [Ca2+]水平升高。因此，由于 SERCA 抑制而不是 RyR 激活，与使用 4CmC（≥1mM）相关的任何 [Ca2+]水平的增加都可能导致非特异性 Ca2+变化。
