A Thapsigargin-Resistant Intracellular Calcium Sequestering Compartment in Rat Brain

Abstract : Calcium plays a central regulatory role in the normal function of all cells. Electrical, secretory, and metabolic activities of cells in the brain require fine control over ionized cytoplasmic calcium levels. Intracellular calcium levels are controlled by a diverse set of cytoplasmic and membrane-associated mechanisms including calcium binding proteins, channels, pumps, and exchangers. The endoplasmic reticulum (ER) calcium stores have a major impact on neuronal intracellular signaling. Most of the ER in neurons and glia appears to accumulate calcium by energy driven ion pumps known as sarco/endoplasmic reticulum calcium ATPases (SERCAs), which are potently and selectively inhibited by thapsigargin. However, the ER represents a heterogeneous network of cisternae in which calcium-accumulating subcompartments may be spatially and functionally distinct. We describe here the characterization of a novel calcium accumulating subcompartment of rat brain ER, which is insensitive to thapsigargin. This compartment accumulates calcium in a magnesium and ATP-D-dependent manner and is distinguished from thapsigargin- sensitive calcium pools with respect to anion permeability inhibitor sensitivity, sensitivity to calcium mobilizers, and brain anatomical distribution.