Expression of Activated PKC Epsilon (PKC ε) Protects the Ischemic Heart, without Attenuating Ischemic H+ Production

PKC ε is a PKC isoform that translocates during preconditioning and may mediate cardioprotection. To investigate whether PKC ε activation is cardioprotective, Langendorff-perfused hearts from wild-type (WT) mice and from mice expressing constitutively active mutant PKC ε were subjected to 20 min ischemia and 40 min reperfusion while31P NMR spectra were acquired. Pre-ischemic glycogen levels were similar in WT and PKCε hearts. During ischemia, ATP fell less in PKC ε than in WT hearts. Ischemic intracellular pH, however, was similar in WT and PKC ε hearts. During reperfusion, recovery of contractile function and ATP were greater in PKCε than WT hearts. In conclusion, expression of activated PKC ε protected hearts from post-ischemic energetic and contractile dysfunction, consistent with the proposed cardioprotective role of PKC ε. Protection occurred in the PKC ε hearts without attenuation of ischemic H+ production, implying that, at least in this ischemic model, reduced acidification during ischemia is not necessary for cardioprotection.