Laboratory of Molecular Sensors. Centro Interdisciplinario de Neurociencia de Valparaíso.
Investigation area: ion channels biophysics and physiology
B.S Biotechnology, University of Chile ( 2003 )
Molecular Biotechnology Engineer, University of Chile ( 2005 )
PhD in Sciences, University of Chile ( 2008 ).
Pasaje Harrington 287 Playa Ancha. Valparaíso, Chile.
One of the most fundamental sensorial abilities of living organisms is temperature sensing. Failures to avoid noxious cold or heat could lead to tissue damage or fatal injury. Neurons capable of discriminating temperatures ranging from extreme cold (∼ –10°C) to extreme heat (∼ 60°C), are located in trigeminal ganglia, and in dorsal root ganglia innervating the head and the rest of the body, respectively. Temperature-sensitivity is possible by the expression of a subset of transient receptor potential (TRP) ion channels that are activated by cold or hot temperatures with different thresholds. Temperature sensation is intimately associated to nociceptive signaling in physiological and pathological conditions; hence, thermoTRP channels have been a focus of biomedical research as target for pain relief. To determine how this class of ion channels sense temperature represent a therapeutic opportunity for painful conditions where thermoTRP channels activity is altered. We are particularly focused on the TRP melastatin receptor type 8 (TRPM8) and TRP vanilloid type 1 (TRPV1) channels, which has been identified as the cold and heat receptors transducers in vivo. These channels are involved in inflammatory and neuropathic pain states and are overexpressed in various cancer types. The activation of TRPM8 and TRPV1, has an analgesic effect, that may counteract the symptoms of neuropathic pain. As temperature and pain responses are intimately linked, understanding how temperature is sensed, and where the temperature sensor is in the protein, has biological and clinical relevance, and opens a window for drug discovery. The role of lipids in thermoTRP and BK channels gating is also a focus of our research.
To study thermoTRP channels we use biophysical (electrophysiological and thermodynamic analysis, patch fluorometry, tmFRET) and computational (molecular modeling) approaches.
- Díaz-Franulic I, Raddatz N, Castillo K, González-Nilo FD, Latorre R. 2020. A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels. Proc Natl Acad Sci U S A. DOI:1073/pnas.2004303117.
- Ramírez-Barrantes R, Carvajal-Zamorano K, Rodriguez B, Cordova C, Lozano C, Simon F, Díaz P, Muñoz P, Marchant I, Latorre R, Castillo K, Olivero P. 2020. TRPV1-Estradiol Stereospecific Relationship Underlies Cell Survival in Oxidative Cell Death. Front Physiol. DOI: 3389/fphys.2020.00444.
- Lorenzo-Ceballos Y, Carrasquel-Ursulaez W, Castillo K, Alvarez O, Latorre R. 2019. Calcium-driven regulation of voltage-sensing domains in BK channels. Elife 8: e44934. DOI: 7554/eLife.44934.
- Castillo K, Diaz-Franulic I, Canan J, Gonzalez-Nilo F, Ramon Latorre. Thermally-activated TRP channels: Molecular sensor for temperature detection. 2018. Physical Biology 15(2): 021001. DOI: 1088/1478-3975/aa9a6f.
- Ramón Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V. Sepulveda, Fernando González-Nilo, Carlos Gonzalez and Osvaldo Alvarez. Molecular determinants of BK cannel functional diversity and functioning. Physiological Reviews 97(1): 39-87. DOI: 10.1152/physrev.00001.2016.