physiology institute, CISNe, PBC, UACh
We are grateful for all the generous funding that support our research over the years
Sensory input together with perception mechanisms govern our navigation through the world. The Brauchi laboratory at Universidad Austral de Chile is devoted to study the activation and modulation of the cellular components that participate in the detection of external stimuli. In particular, we are focused on the activation and modulation of molecular sensors, the evolution of TRP ion channels proteins, and the biophysical properties of ion channels. We are also interested on the development of novel experimental approaches including optical methods and platforms for image analysis. On our research we use a combination of electrophysiological, optical, biochemical, and molecular biological techniques.
The evolution of TRP channel proteins
Transient Receptor Potential ion channels are important in sensory physiology; TRP channels enable moving animals to sense diverse stimuli such as light, pressure, smell, taste, sound, and temperature. Sensory modalities are fundamental for navigation through an ever changing environment. TRP channel coding sequences present in several unicellular genomes provide a unique oportunity for comparative studies.
Gating and modulation of TRP channels
Membrane voltage, ligand binding, mechanical force and temperature can all induce conformational changes that open ion channel pores. A key question in understanding ion channel function is how the protein domains involved in sensing stimuli (sensors) communicate with the pore to gate its opening.
TRP channels function as signal integrators that receive energy from different sources (e.g. thermal heating or cooling, changes in membrane voltage, PI(4,5)P2 binding, binding of chemical agonists and antagonists) and respond by changing their open probability. This obviously extends to intracellular TRP channels, which may sense yet more varied forms of input stimuli. This characteristic polymodal activation difficult the elucidation of a general mechanism for TRP channel activation providing a very interesting biophysical problem to solve.
Ion channel targeting and cellular control of receptor density
In order to achieve the high spatial and temporal regulation that may be necessary to transduce sensory stimuli, TRP channels must be targeted to specific locations. Tight control of TRP channel trafficking and delivery to various membrane compartments is thus a potentially critical step in regulating the flow of sensory information. Modulation of TRP channel distribution and availability by vesicular translocation has been reported as a regulatory mechanism for TRP channel function. Plasma membrane (PM) vesicle insertion regulates the number of functional thereby dictating total ionic flux and the cellular consequences of TRP channel function.
The control of TRP channel activity and cellular sensing
Mammalian TRP channel proteins are polymodal cation channels with essential roles in cellular sensing. Other than a loose sequence homology, predicted channel architecture, and a common poor cation selectivity, there are no particular features defining the TRP family. The 28 known mammalian TRP channels are grouped by homology into six sub-families named C, M, V, A, P, and ML, for canonical, melastatin related, vanilloid binding, ankyrin repeat, polycystin, and mucolipin, respectively. By integrating multiple stimuli they supply signal amplification through calcium permeation and membrane depolarization. Cooperativity intrinsic to TRP channels may result in allosteric coupling of distinct activation stimuli. Additionally, has been observed that TRP-mediated cellular response can be modulated by exocytosis and cell trafficking. Our research is focused on the elements that control the activity of temperature-activated TRP channels (thermoTRPs).