Ion channels are responsible for many physiological processes including neuronal signaling and muscle contraction, and they exert their basic function by regulating the flow of physiological ion across the cell membrane through a complex mechanism of opening and closing known as gating. My research interest resides in the area of ion channel functioning - with emphasis on the ways channel gating kinetics and trafficking can be affected by physiological mechanisms such as channel activity itself, or by agonists and modulators. To this aim we express ligand-gated or voltage-gated ion channels in a relatively simple, single-cell system, the Xenopus frog oocyte. After microinjection of cRNA or cDNA encoding for the desired channels, the oocytes synthesize and incorporate functional channels into their surface membrane.
Most of my recent work involves the development of an innovative optical technique we named “Optical Patch-clamp Recording” which uses total internal reflection fluorescence microscopy (TIRFM) to obtain simultaneous and independent recording from numerous open ion channel via imaging Ca 2+ flux through an open channel. The technique allows simultaneous studies of channel gating, channel location, and motility with high spatial (50 nm) and temporal resolution (2 ms). For example, we have shown that when expressed in Xenopus oocytes, N-type channel can display divergent open probability, with individual channels displaying transitions between low and high frequency opening, that they are homogeneously distributed and rigidly anchored to the oocyte membrane. More recently, we also showed that muscle abgd and neuronal a 4 b 2 nAChRs display random spatial distribution, and that both receptor types are immobile in the oocyte membrane. Interestingly whereas muscle type nAChRs show a single conducting state, a single neuronal type receptor can switch between two conductance states. Future goals in my research interest will involve the use of Optical Patch-clamp Recording to study the many ion channels responsible for many neurological and muscular disorder (such as chronic pain, Parkinson’s Disease and Myasthenia Gravis ) to better understand their physiology and to gain more knowledge about development of future drug treatments for the neurological disorders that have no cure today.