Protein kinase C-mediated calcium signaling as the basis for cardiomyocyte plasticity

Protein kinase C is the superfamily of intracellular effector molecules which control crucial cellular functions. Here, we for the first time did the percentage estimation of all known PKC and PKC-related isozymes at the individual cadiomyocyte level. Broad spectrum of PKC transcripts is expressed in the left ventricular myocytes. In addition to the well-known 'heart-specific' PKCα, cardiomyocytes have the high expression levels of PKCN1, PKCδ, PKCD2, PKCε. In general, we detected all PKC isoforms excluding PKCη. In cardiomyocytes PKC activity tonically regulates voltage-gated Ca²⁺-currents, intracellular Ca²⁺ level and nitric oxide (NO) production. Imidazoline receptor of the first type (I₁R)-mediated induction of the PKC activity positively modulates Ca²⁺ release through ryanodine receptor (RyR), increasing the Ca²⁺ leakage in the cytosol. In cardiomyocytes with the Ca²⁺-overloaded regions of > 9-10 μm size, the local PKC-induced Ca²⁺ signaling is transformed to global accompanied by spontaneous Ca²⁺ waves propagation across the entire cell perimeter. Such switching of Ca²⁺ signaling in cardiac cells can be important for the development of several cardiovascular pathologies and/or myocardial plasticity at the cardiomyocyte level.