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 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.
Al-Mousa
Fawaz
F
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK B15 2TT, United Kingdom.
Michelangeli
Francesco
F
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003408:Cresols / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine
D003408:Cresols; D019837:Ryanodine Receptor Calcium Release Channel; C006984:chlorocresol; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium