Expression of activated PKC epsilon (PKCε) protects the ischemic heart, without attenuating ischemic H⁺ production

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