Daniel J. Calvo, Ph.D.

Research

Physiology, pharmacology and biophysics of ionotropic GABA receptors. Our lab studies the signaling mechanisms for neuronal inhibition in the central nervous system mediated by the amino acid g-aminobutyric acid (GABA). The main focus of our research is on GABAA and GABAC receptors which are ligand-gated ion channels. GABAA receptors are transmembrane proteins formed by five subunits out of sixteen different isoforms encoded by distinct genes. Seven GABAA receptor subunit types have been recognized, namely: a, b, g, d, e, p and t. GABAC receptors are also pentameric proteins, they are assembled as homomeric or heteromeric channels composed exclusively by subunits (r1, r2, r3). The physiological, pharmacological and biophysical properties of ionotropic GABA receptors depend critically on their subunit composition. GABAA receptors are more diverse and underlie fast, inhibitory, synaptic transmission and have an important role in the control of neuronal excitability. They are also targets for clinically relevant drugs. GABAC receptors are highly expressed in hippocampus and visual pathways, but their role is less understood. In the brain, disfunction in the GABAergic systems can lead to brain disorders (Epilepsy, Parkinson and Huntington disease, etc). At present we are studying the modulation of neurotransmission mediated by GABAA and GABAC receptors by redox mechanisms. The final aim of our research is to improve our understanding on the physiological, pharmacological and biophysical properties of GABAA and GABAC receptors and the functional significance of their heterogeneity. Our work combine molecular biology and electrophysiological techniques such as heterologous expression of recombinant synaptic receptors and ionic channels, followed by two electrode voltage-clamp recording in Xenopus laevis oocytes and somatic whole-cell patch-clamp electrophysiological recordings of synaptic currents and neuronal activity in acute brain slices.