Research in the Zimmermann Lab at the Department of Anesthesiology at Friedrich-Alexander University Erlangen-Nürnberg focusses on the physiological role of ion channels in the somatosensory system. This relates to delineating the function of ion channels in thermo- and nociceptive transduction and electrogenesis as well as in the related pathophysiology.
The NaV1.8 sodium channel subtype functions as cold-resistant ignition on nociceptors and is also able to shape heat-resistant action potentials above 45°C. Unlike other fast-gated and low-threshold sodium channel subtypes that become inactivated by cold or hot temperatures, Nav1.8 appears resistant and increases the excitability of nociceptors at noxious cold and hot temperatures. Nav1.9, in contrast is tuned to provide a persistent current and enables nociceptors to produce action potentials in response to fast-rising temperatures and thereby to protect us from heat-induced tissue damage.
Touska F, Turnquist B, Vlachova V, Reeh PW, Leffler A, Zimmermann K. Heat-resistant action potentials require TTX-resistant sodium channels NaV1.8 and NaV1.9. J Gen Physiol 150: 1125-1144, 2018.
The voltage-gated Kv7.2/3 channels are suprathreshold amplifiers of TRPM8-mediated cold transduction. Triggered by the activation of the menthol-receptor TRPM8 the channels are progressively closed by cold, thereby increasing the cold transduction current in the nociceptive endings of the skin. Menthol also proves to be a potent blocker of these important, pan-neuronal potassium channels and intrinsically enhances its TRPM8 agonism through this effect.
Vetter I, Hein A, Sattler S, Hessler S, Touska F, Bressan E, Parra A, Hager U, Leffler A, Boukalova S, Nissen M, Lewis RJ, Belmonte C, Alzheimer C, Huth T, Vlachova V, Reeh PW, Zimmermann K. Amplified cold transduction in native nociceptors by M-channel inhibition. The Journal of neuroscience: the official journal of the Society for Neuroscience 33: 16627-16641, 2013.
The noxious cold transduction channel TRPA1 seems to be a central molecule in the development of pathological cold allodynia such as induced by certain fish toxins, called ciguatoxins. Ciguatoxins come from tropical dinoflagellates and accumulate in fish meat via the food chain and lead to ciguatera for which a long-lasting cold allodynia is pathognomonic. These potent sodium channel poisons causes membrane potential oscillations that lead to a sensitization of the temperature sensitivity of TRPA1 which turns temperatures that are normally pleasantly cool into the burning painful feeling of freezing cold. TRPA1 deficient mice show significantly reduced cold allodynia.
Vetter I, Touska F, Hess A, Hinsbey R, Sattler S, Lampert A, Sergejeva M, Sharov A, Collins LS, Eberhardt M, Engel M, Cabot PJ, Wood JN, Vlachova V, Reeh PW, Lewis RJ, Zimmermann K. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling. The EMBO journal 31: 3795-3808, 2012.
In order to more closely research the contribution of individual ion channels to overall temperature sensitivity we developed a new scientific instrument which allows to phenotype thermal preference behavior without experimenter interference. This device allowed us to identify the contribution of TRPM8 and TRPA1 as synergistic in cold temperature perception and absence of both channels results in a much delayed cold avoidance. It can be purchased from Ugo Basile.
Touska F, Winter Z, Mueller A, Vlachova V, Larsen J, Zimmermann K. Comprehensive thermal preference phenotyping in mice using a novel automated circular gradient assay. Temperature (Austin) 3: 77-91, 2016.
Currently we aim to understand the function of cold-sensitive TRP-channels to variable cold sensitivity and how peripheral cold sensing connects with thermoregulation, metabolism and CNS processing. We are also interested in understanding the molecular pathophysiology of painful cold sensing and cold allodynia specifically with respect to individual susceptibility differences, but also in particular cold sensitive organs such as teeth.
For a list of all publications go to google scholar
Laura Bernal, Pamela Sotelo-Hitschfeld, Filip Touska
Zoltan Winter, Aklesso Kadala, Ricardo Kusuda (FAPESP Fellow, Universidade de São Paulo, Ribeirão Preto, Brazil)
Aaron Tragl, Gregor Neussel, Patrick Burke, Alexander Kapp, Ziad Ahmad, Anneka Eisenblätter, Philipp Gruschwitz, Antonia Fitzek, Stefanie Eger
Viktorie Vlachova, Czech Academy of Sciences, Prague, Czech Republic
Sebastian Brauchi, Universidad Austral de Chile, Valdivia, Chile
Carolina Roza, Universidad de Alcalá, Madrid, Spain
Gary Peltz, Stanford University, Palo Alto, CA, USA
Jeff Mogil, Pain Genetics, McGill University, Montreal, Canada
Simon Brookes and Rochelle Peterson, Human Physiology, Flinders University, Adelaide, Australia
Jochen Lennerz, Department of Pathology, MGH and Harvard Medical School, Boston, USA