Publication Date

2014

Document Type

Thesis

Committee Members

Norma Adragna (Committee Member), David Cool (Committee Member), Mauricio Di Fulvio (Advisor), Peter Lauf (Committee Member)

Degree Name

Master of Science (MS)

Abstract

The Slc12a5 gene encodes the neuron-specific electroneutral K+Cl- cotransporter-2 (KCC2), a constitutively active Cl- extruder. In mature neurons, KCC2 functionally predominates over other members of the Slc12a family, particularly the Na+K+2Cl- cotransporter-1 (NKCC1), a ubiquitous Cl- loader. Therefore, KCC2 keeps and maintains the intracellular chloride concentration ([Cl-]i) below values predicted by thermodynamic equilibrium and in doing so, KCC2 plays a key role in neuron physiology: it makes possible the inhibitory action of neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine. Neurons and insulin-secreting pancreatic ß-cells share many genes and functions. Indeed, neuron-specific genes have been also found in ß-cells whereas both neurons and ß-cells are electrically excitable. Our experiments demonstrate that, like in neurons, KCC2 is expressed in ß-cells and suggest that the functional balance NKCC1/KCC2 modulates insulin secretion in response to glucose.

Page Count

114

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2014


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