Cellular signalling
Principal Investigator
Bryndis Birnir, Uppsala University
Bryndis.Birnir@neuro.uu.se
Research area description
Our main interest is the role of gamma-aminobutyric acid (GABA) and GABA-activated ion channels (GABA channels) in physiology.
Our quest is to understand the function of GABA and the extrasynaptic-like channels in the brain, in the endocrine pancreas and in lymphocytes. How does the GABA signaling come about, what are the channels made of, how do they operate and how can they be modulated.
These channels are targeted by drugs important in the clinic such as benzodiazepines, barbiturates and anesthetics. They are important in healthy individuals but do also have a role in diseases like type 1 and type 2 diabetes.
GABA is released from the insulin-containing beta cells and activates GABA channels on the beta and the glucagon-secreting alpha cells resulting in modified hormone secretion. However, it is not known what the effective physiological concentration of GABA in the endocrine pancreas is. Setting precisely the GABA concentration in the islet may be critical:
- for the right balance between the insulin and the glucagon concentration in the blood
- for protecting the beta cells from invading toxic lymphocytes.
In intact human and rodent islets we attempt to construct the islet GABA affinity curve and determine the GABA sensitivity of the islet cells recording from single-channel (single molecule) recordings, similar to what we have done in hippocampampal neurons (Lindquist and Birnir, 2006; Zhet et al., 2011).
If we are successful, the results will tell us what the functional GABA concentration range is in human islets and can potentially be used in preventive medicine regarding type 1 and type 2 diabetes and to develop new medicine and therapies to treat these diseases.