Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

The Ca2+-binding proteins parvalbumin (PV) and calbindin D-28k (CB) are key players in the intracellular Ca2+-buffering in specific cells including neurons and have profound effects on spatiotemporal aspects of Ca2+ transients. The previously observed increase in mitochondrial volume density in fast-twitch muscle of PV−/− mice is viewed as a specific compensation mechanism to maintain Ca2+ homeostasis. Since cerebellar Purkinje cells (PC) are characterized by high expression levels of the Ca2+ buffers PV and CB, the question was raised, whether homeostatic mechanisms are induced in PC lacking these buffers. Mitochondrial volume density, i.e. relative mitochondrial mass was increased by 40% in the soma of PV−/− PC. Upregulation of mitochondrial volume density was not homogenous throughout the soma, but was selectively restricted to a peripheral region of 1.5 μm width underneath the plasma membrane. Accompanied was a decreased surface of subplasmalemmal smooth endoplasmic reticulum (sPL-sER) in a shell of 0.5 μm thickness underneath the plasma membrane. These alterations were specific for the absence of the “slow-onset” buffer PV, since in CB−/− mice neither changes in peripheral mitochondria nor in sPL-sER were observed. This implicates that the morphological alterations are aimed to specifically substitute the function of the slow buffer PV. We propose a novel concept that homeostatic mechanisms of components involved in Ca2+ homeostasis do not always occur at the level of similar or closely related molecules. Rather the cell attempts to restore spatiotemporal aspects of Ca2+ signals prevailing in the undisturbed (wildtype) situation by subtly fine tuning existing components involved in the regulation of Ca2+ fluxes.