The Role of Plasma Membrane Ca2+-ATPase in Excitable Cells Signaling

Abstract

During the last decade the mechanisms of Ca2+ regulation in the brain have been extensively investigated in a variety of neural cells. These investigations demonstrate that intraneuronal Ca2+ participate in the multiple controls of important neural functions, like excitability, neurotransmitters release or long-term changes in synaptic efficacy. Moreover, there is a significant number of data confirming that the impairment of calcium homeostasis is closely linked with aging and several brain disorders. The plasma membrane Ca2+-ATPase (PMCA) is a ubiquitously expressed protein, which constitutes a high affinity system extruding Ca2+ outside the cell and maintains the intracellular Ca2+ in the submicromolar range in a resting state. In neuronal tissues more than 26 transcripts of the four separate PMCA genes are distributed in a region specific manner. Differences in the structure and localization of PMCA variants are thought to correlate with specific regulatory properties and may have consequences for proper Ca2+ signaling or for the response to the brain malfunction. Below some new aspects of the Ca2+-ATPase modulation in physiological and pathological conditions will be discussed which may influence neuronal calcium signaling.