Calcium Ion Homeostasis in the Aging Brain: Regulation of Voltage-Dependent Calcium Channels

The tuning of neuronal networks is controlled by a number of processes that are in turn strictly controlled by cytosolic free Ca2++ ions. Short-term functions such as neurotransmitter release and enzymatic activity, and long-term mechanisms such as cytoskeletal integrity, neuronal plasticity, and even gene expression, depend on a rise in free intraneuronal calcium levels.1 Although a “transient” rise in calcium concentration is of physiologic significance, a prolonged calcium increase in the cytoplasm, if not buffered properly, can lead to cell membrane derangement (overstimulation of calcium-dependent kinases, lipases, and proteases) that may end in cell death.2 Intracellular calcium “oscillations” represent an additional mechanism for neuronal and endocrine signaling,3 which has been investigated in particular in nonexcitable cells.4