GABAergic neurotransmission depends upon the transmembrane Cl concentration gradient that exists at the synapse. The intracellular Cl concentration in CNS and PNS neurons is regulated, in part, by cation-chloride cotransport mechanisms such as Na-K-2Cl and K-Cl cotransporters. For example, the inward Na-K-2Cl cotransporter is highly expressed in immature CNS neurons, resulting in a high intracellular Cl- concentration and GABA depolarizing or excitatory responses. In contrast, mature CNS neurons have low Na-K-2Cl cotransporter and high K-Cl cotransporter leading to low intracellular Cl- and GABA hyperpolarizing or inhibitory responses.
The Delpire Laboratory is creating and studying genetically-modified mouse models of the cotransporters and of proteins that regulate them. The work, involves molecular biology, physiology, electrophysiology and behavior. These studies have significance in pain perception, hyper-excitability and epilepsy, nerve conduction, peripheral neuropathy and paraplegia. In the 2009-2010 academic year, the laboratory graduated one student in the neuroscience program, published nine research articles, two scientific reviews, nine meeting abstracts, a book, and four book chapters. The laboratory, with the support of the departments of Anesthesiology and Molecular Physiology & Biophysics, also hosted the first annual meeting of the Tennessee Physiological Society.