Abstract
BackgroundThe gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain. The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored.Principal FindingsWe have therefore studied the potential existence of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes using human brain tissue samples in contrast to cultured astrocytes that had primarily been used in the past. It was thus found that secretory granule marker proteins chromogranins and secretogranin II localize in the large dense core vesicles of astrocytes, thereby confirming the large dense core vesicles as bona fide secretory granules. Moreover, consistent with the major IP3-dependent intracellular Ca2+ store role of secretory granules in secretory cells, secretory granules of astrocytes also contained all three (types 1, 2, and 3) IP3R isoforms.SignificanceGiven that the secretory granule marker proteins chromogranins and secretogranin II are high-capacity, low-affinity Ca2+ storage proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+ channels, i.e., increase both the mean open time and the open probability of the channels, these results imply that secretory granules of astrocytes function as the IP3-sensitive intracellular Ca2+ store.
Highlights
Astrocytes are known to secrete a number of signaling molecules that participate in the cell-to-cell communication, involving both neurons and glial cells [1,2,3,4,5,6,7]
Analogous to the neurotransmitters stored in synaptic vesicles of neurons, small signaling molecules of astrocytes are traditionally thought to be stored in small synaptic-like vesicles and released in a regulated fashion, which in turn participate in neuron-glial cell communication in the brain [4,14,20,21,22,23,24,25,26,27]
Antibodies The polyclonal anti-rabbit chromogranin A (CGA), chromogranin B (CGB), secretogranin II (SgII) antibodies were raised against purified intact bovine CGA, CGB and SgII [49,50], and affinity purified against bovine CGA, recombinant CGB and SgII [51]
Summary
Astrocytes are known to secrete a number of signaling molecules that participate in the cell-to-cell communication, involving both neurons and glial cells [1,2,3,4,5,6,7] Of these signaling molecules, ATP, glutamate, D-serine, neuropeptide Y (NPY), called gliotransmitters, are known. The gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored
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