PKC-dependent Preconditioning with Norepinephrine Protects Sarcoplasmic Reticulum Function in Rat Trabeculae Following Metabolic Inhibition

• Published in: Journal of molecular and cellular cardiology 1999-05, Vol.31 (5), p.1083-1094
• Main Authors: Musters, René J.P., van der Meulen, Esther T., Zuidwijk, Marian, Muller, Alice, Simonides, Warner S., Banerjee, Anirban, van Hardeveld, Cornelis
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Ca2+-overload; Calcium - metabolism; Homeostasis; Ischemic Preconditioning, Myocardial; Male; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Myocardial Contraction - drug effects; Norepinephrine; Norepinephrine - therapeutic use; Preconditioning; Protein kinase C; Protein Kinase C - metabolism; Rats; Rats, Wistar; Ryanodine - therapeutic use; Sarcoplasmic Reticulum - drug effects; Sarcoplasmic Reticulum - metabolism; Sarcoplasmic reticulum function
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1999.0940

The authors have previously shown that norepinephrine (NE) pretreatment attenuates Ca2+overloading in cardiac rat trabeculae during metabolic inhibition, and improves contractile function during a subsequent recovery period. The present study investigated: (i) whether protection of sarcoplasmic reticulum (SR) function during metabolic inhibition (MI) is involved in the preconditioning-like effect of NE-pretreatment, and (ii) whether or not this process is PKC-dependent. A 15 min preincubation period was used with 1μmol/l exogenous NE to precondition isolated, superfused rat trabeculae against contractile dysfunctioning following 40 min of MI in 2 mmol/l NaCN containing Tyrode (gassed with 95% O2/5% CO2; pH 7.4, 24°C) without glucose at 1-Hz stimulation frequency. Contractile recovery was studied during a subsequent 60 min recovery period (RP) in glucose containing Tyrode at 0.2 Hz. Force and intracellular free calcium ([Ca2+]ii) were monitored throughout the experimental protocol. Pretreatment of trabeculae with NE (group NE) substantially diminished the Ca2+rise from the onset of rigor development during MI, compared to preparations which were pretreated with NE, in the presence of specific PKC blocker chelerythrine (2μmol/l; group NE+CHEL). After 40 min of MI, resting [Ca2+]iin group NE and NE+CHEL was increased to 0.50±0.03 and 2.08±0.20μmol/l, respectively (P