TY - JOUR
T1 - Effects of pharmacological preconditioning with U50488H on calcium homeostasis in rat ventricular myocytes subjected to metabolic inhibition and anoxia
AU - Ho, J. C.S.
AU - Wu, S.
AU - Kam, K. W.L.
AU - Sham, J. S.K.
AU - Wong, T. M.
PY - 2002/11
Y1 - 2002/11
N2 - 1. The effects of pharmacological preconditioning with U50488H (U 50), a selective κ-opioid receptor agonist, on Ca 2+ homeostasis in rat ventricular myocytes subjected for 9 min to metabolic inhibition (MI) and anoxia (A), consequences of ischaemia, were studied and compared with those of preconditioning with brief periods of MI/A. 2. Precondition with 30 μM of U 50 for three cycles of 1 min each cycle separated by 3 min of recovery (UP) significantly increased the percentage of non-blue cells following MI/A. The effect of UP is the same as that of preconditioning with an inhibitor of glycolysis and an oxygen scavenger for three 1-min cycles separated by three-minute recovery (MI/AP). The results indicate that like MI/AP, UP also confers cardioprotection. 3. MI/A increased intracellular Ca 2+ ([Ca 2+] i) and reduced the amplitude of caffeine-induced [Ca 2+] i transients, an indication of Ca 2+ content in the sarcoplasmic reticulum (SR). MI/A also reduced the electrically-induced [Ca 2+] i transient, that indicates Ca 2+-release during excitation-contraction coupling, and Ca 2+ sparks in unstimulated myocytes, that indicates spontaneous Ca 2+-release from SR. It also prolonged the decline of the electrically-induced [Ca 2+] i transient and slowed down the recovery of the electrically-induced [Ca 2+] i transient after administration of caffeine. In addition, MI/A prolonged the decline of caffeine induced [Ca 2+] i transient, an indication of Na +-Ca 2+ exchange activity, and UP prevented it. So UP, that confers cardioprotection, prevented the changes induced by MI/A. With the exception of Ca 2+-spark, which was not studied, the effects of MI/AP are the same as those of UP. 4. It is concluded that pharmacological preconditioning with U 50, that confers immediate cardioprotection, prevents changes of Ca 2+ homeostasis altered by MI/A in the rat heart. This may be responsible, at least partly, for the cardioprotective action. 5. The study also provided evidence that MI/A causes mobilization of Ca 2+ from SR to cytoplasm causing Ca 2+-overload which may be due to reduced Ca 2+-uptake by SR. MI/A also reduces spontaneous and electrically induced Ca 2+ release from SR.
AB - 1. The effects of pharmacological preconditioning with U50488H (U 50), a selective κ-opioid receptor agonist, on Ca 2+ homeostasis in rat ventricular myocytes subjected for 9 min to metabolic inhibition (MI) and anoxia (A), consequences of ischaemia, were studied and compared with those of preconditioning with brief periods of MI/A. 2. Precondition with 30 μM of U 50 for three cycles of 1 min each cycle separated by 3 min of recovery (UP) significantly increased the percentage of non-blue cells following MI/A. The effect of UP is the same as that of preconditioning with an inhibitor of glycolysis and an oxygen scavenger for three 1-min cycles separated by three-minute recovery (MI/AP). The results indicate that like MI/AP, UP also confers cardioprotection. 3. MI/A increased intracellular Ca 2+ ([Ca 2+] i) and reduced the amplitude of caffeine-induced [Ca 2+] i transients, an indication of Ca 2+ content in the sarcoplasmic reticulum (SR). MI/A also reduced the electrically-induced [Ca 2+] i transient, that indicates Ca 2+-release during excitation-contraction coupling, and Ca 2+ sparks in unstimulated myocytes, that indicates spontaneous Ca 2+-release from SR. It also prolonged the decline of the electrically-induced [Ca 2+] i transient and slowed down the recovery of the electrically-induced [Ca 2+] i transient after administration of caffeine. In addition, MI/A prolonged the decline of caffeine induced [Ca 2+] i transient, an indication of Na +-Ca 2+ exchange activity, and UP prevented it. So UP, that confers cardioprotection, prevented the changes induced by MI/A. With the exception of Ca 2+-spark, which was not studied, the effects of MI/AP are the same as those of UP. 4. It is concluded that pharmacological preconditioning with U 50, that confers immediate cardioprotection, prevents changes of Ca 2+ homeostasis altered by MI/A in the rat heart. This may be responsible, at least partly, for the cardioprotective action. 5. The study also provided evidence that MI/A causes mobilization of Ca 2+ from SR to cytoplasm causing Ca 2+-overload which may be due to reduced Ca 2+-uptake by SR. MI/A also reduces spontaneous and electrically induced Ca 2+ release from SR.
KW - Anoxia
KW - Ca homeostasis
KW - Ca spark
KW - Metabolic inhibition
KW - Preconditioning
KW - Sarcoplasmic reticulum
KW - U50488H
KW - Ventricular myocyte
KW - κ-opioid receptor
UR - http://www.scopus.com/inward/record.url?scp=0036854465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036854465&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0704945
DO - 10.1038/sj.bjp.0704945
M3 - Article
C2 - 12411403
AN - SCOPUS:0036854465
SN - 0007-1188
VL - 137
SP - 739
EP - 748
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -