We have a long standing interest in the study of molecular mechanisms of modulation of voltage gated K+ (Kv) channels by interaction with signaling molecules. We were first to describe modulation of a brain Kv channel by major protein components of the exocytotic machinery. Since then our main focus is the role of Kv channels in transmitter and hormone release from neuroendocrine and pancreatic islet β cells, finding that it may be far more than just repolarizing membrane potential: independent of K+ currents but mediated by protein-protein interactions with the SNARE proteins (syntaxin 1A, SNAP-25 and VAMP2 (synaptobrevin)), essential to the process of Ca2+ regulated release. We find that the dual actions of the channel, through its currents and via its interaction with the SNAREs, in combination, may reinforce the known activity dependence of dense core vesicle exocytosis and relevant to therapy of type-2 diabetes.
- Two-electrode voltage clamp and patch clamp techniques for the study of whole cell and single channel currents.
- Membrane capacitance and amperometry measurements for the study of exocytosis.
- co-immunoprecipitation, immunohystochemistry, recombinant protein chemistry, etc, for the study of in vivo and in vitro protein-protein interactions.
- Fluorescence Resonance Energy Transfer (FRET) for the study of protein-protein interactions.
- Total Internal Reflection Fluorescence Microscopy (TIRFM) for the study of neurotransmitter vesicles behavior.
Current research projects in the lab:
1) Study of the novel role of Kv2.1 potassium channel in insulin secretion from pancreatic islet β cells, as a target for novel drug design for the treatment of type-2 diabetes.
2) Study of structure-function and modulations by presynaptic modulators, like syntaxin 1A and calmoidulin, of Kv channels, specifically KCNQ2 and KCNQ3, important in axonal and synaptic excitability.
3) Investigating the conformational changes of Syntaxin 1A during exocytosis, using novel fluorescent probes constructed in the lab, and their implications to exocytosis-related events, in general, and for Kv2.1-induced facilitation of exocytosis.