Ischemic postconditioning and pinacidil suppress calcium overload in anoxia-reoxygenation cardiomyocytes via down-regulation of the calcium-sensing receptor.
Ischemic postconditioning (IPC) and ATP sensitive potassium channel (KATP) agonists (e.g. pinacidil and diazoxide) postconditioning are effective methods to defeat myocardial ischemia-reperfusion (I/R) injury, but their specific mechanisms of reducing I/R injury are not fully understood. We observed an intracellular free calcium ([Ca2+]i) overload in Anoxia/reoxygenation (A/R) cardiomyocytes, which can be reversed by KATP agonists diazoxide or pinacidil. The calcium-sensing receptor (CaSR) regulates intracellular calcium homeostasis. CaSR was reported to be involved in the I/R-induced apoptosis in rat cardiomyocytes. We therefore hypothesize that IPC and pinacidil postconditioning (PPC) reduce calcium overload in I/R cardiomyocytes by the down-regulation of CaSR. A/R model was established with adult rat caridomyocyte. mRNA and protein expression of CaSR were detected, IPC, PPC and KATP's effects on [Ca2+]iconcentration was assayed too. IPC and PPC ameliorated A/R insult induced [Ca2+]ioverload in cardiomyocytes. In addition, they down-regulated the mRNA and protein level of CaSR as we expected. CaSR agonist spermine and KATP blocker glibenclamide offset IPC's effects on CaSR expression and [Ca2+]imodulation. Our data indicate that CaSR down-regulation contributes to the mitigation of calcium overload in A/R cardiomyocytes, which may partially represents IPC and KATP's myocardial protective mechanism under I/R circumstances.
Department of Anesthesiology, Zunyi Medical College, Zunyi, Guizhou, China.|Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical College, Zunyi, Guizhou, China.
Lin
L
Zhang
Department of Anesthesiology, Zunyi Medical College, Zunyi, Guizhou, China.|Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical College, Zunyi, Guizhou, China.
Song
S
Cao
Department of Anesthesiology, Zunyi Medical College, Zunyi, Guizhou, China.|Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical College, Zunyi, Guizhou, China.
Shengli
S
Deng
Department of Anesthesiology, Zunyi Medical College, Zunyi, Guizhou, China.|Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical College, Zunyi, Guizhou, China.
Gang
G
Yao
Department of Anesthesiology, Zunyi Medical College, Zunyi, Guizhou, China.|Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical College, Zunyi, Guizhou, China.
Tian
T
Yu
ATP sensitive potassium channel (KATP); Calcium-sensing receptor (CaSR); Ischemia-reperfusion (I/R) injury; Postconditioning