Projects / Programmes
Fiziologija in patofiziologija astrocita (Slovene)
Code |
Science |
Field |
Subfield |
3.03.00 |
Medical sciences |
Neurobiology |
|
Code |
Science |
Field |
B470 |
Biomedical sciences |
Physiology |
Researchers (2)
no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
1. |
21390 |
PhD Maja Potokar |
Medical sciences |
Researcher |
2005 - 2007 |
0 |
2. |
03702 |
PhD Robert Zorec |
Neurobiology |
Head |
2005 - 2007 |
0 |
Organisations (1)
no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
1. |
1683 |
Celica BIOMEDICAL |
Ljubljana |
1506854 |
0 |
Abstract
The proposed research will aim to address the following specific hypotheses:
1. hypotesis
Trafficking of glutamate transporters to the plasma membrane has been considered recently (Robinson 2002; Fournier et al., 2004), but the mechanisms by which the density of glutamate transporters in glial plasma membrane is regulated are still poorly understood. As for other transporters, such as the GLUT4 glucose transporters, it is likely that glutamate transporters get incorporated into the plasma membrane by exocytosis (Cheng et al., 2002; Karylowski et al., 2004; Zeigerer et al., 2004; Chowdhury et al., 2002). Astrocytes possess several components of secretory apparatus such as synaptobrevin II, cellubrevin, syntaxin, SNAP-23, synaptotagmin IV (Parpura et al., 1995; Hepp et al., 1999; Zhang et al., 2004), essential elements of regulated exocytosis (Jahn and Sudhoff, 1999,). Moreover, it was recently reported that peptide hormones are released from astrocytes via regulated exocytosis (Kržan et al., 2003) and that around 20 µM [Ca2+]i is required for a half maximal increase in membrane surface area increase due to regulated exocytosis (Kreft et al., 2004). Therefore, our hypothesis is that Ca2+-dependent exocytosis may well be a mechanism to affect the density of glutamate transporters in the astrocyte plasma membrane.
2. hypothesis
Hypotonic solutions can evoke the elevation [Ca2+]i in astrocytes (Fischer et al., 1997), which can trigger calcium-regulated exocytosis (Kreft et al., unpublished). Therefore, a hypotonic solution may induce vesicular fusion of glutamate-containing vesicles instead. We will test the hypothesis that stimuli which induce cell swelling include mostly the mechanism of glutamate release through channels/transporters and the hypothesis that activation of metabotropic receptors with chemical transmitters triggers calcium-dependent exocytosis of excitatory transmitter.
3. hypotesis
Cytoskeleton, primarily microtubules and their molecular motors (kinesins in dyneins), have an important role in fast neuronal transport of vesicles (Zigmond et al., 1999). It is clear that for rapid communication between astrocytes and neurons or other neighbouring cells fast transport of substances through cytoplasm of astrocytes, transported with secretory vesicles must be considered. We have shown recently that the velocity of secretory vesicles in astrocytes is similar to velocities of fast transport in neurons (Potokar et al., 2005). The role of different cytoskeleton in astrocytes is, however, unexplored. We will test the hypothesis that different cytoskeletal elements play a role in vesicle transport.