Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5's relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system.

Center for Integrated Diagnostics Department of Pathology Massachusetts General Hospital Harvard Medical School Boston MA USA

Center for Molecular and Cellular Bioengineering Technische Universität Dresden Dresden Germany

Departamento de Biología de Sistemas Facultad de Medicina Universidad de Alcalá Alcalá de Henares Madrid Spain

Department of Anesthesiology Erlangen University Hospital Friedrich Alexander University of Erlangen Nuremberg Erlangen Germany

Department of Cellular Neurophysiology Institute of Physiology Czech Academy of Sciences Prague Czech Republic

Department of Otolaryngology Washington University School of Medicine St Louis MO USA

Department of Pathology Washington University School of Medicine St Louis MO USA

Experimental Pharmacology Center for Molecular Signaling Saarland University School of Medicine Homburg Germany

FARAH Mammalian Transgenics Platform Liège University Liège Belgium

HHMI Cardiovascular Division Boston Children's Hospital and Department of Neurobiology Harvard Medical School Boston MA USA

Institute of Pharmacology University of Heidelberg Heidelberg Germany

Institute of Physiology Faculty of Medicine and Center for Interdisciplinary Studies on the Nervous System Universidad Austral de Chile Valdivia Chile

Millennium Nucleus of Ion Channel associated Diseases Santiago Chile

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Thermosensing ability of TRPC5: current knowledge and unsettled questions

Functional determinants of lysophospholipid- and voltage-dependent regulation of TRPC5 channel