title: Thermal imaging of receptor-activated heat production in single cells.
abstract: Changes in enthalpy (i.e., heat content) occur during the diverse intracellular chemical and biophysical interactions that take place in the life cycle of biological cells. Such changes have previously been measured for cell suspensions or cell-free biochemical extracts by using microcalorimetry, thermocouples, or pyroelectric films, all of which afford minimal spatial or temporal resolution. Here we present a novel thermal imaging method that combines both diffraction-limited spatial (approximately 300 nm) and sampling-rate-limited time resolution, using the temperature-dependent phosphorescence intensity of the rare earth chelate Eu-TTA (europium (III) thenoyltrifluoro-acetonate). With this thermosensitive dye, we imaged intracellular heat waves evoked in Chinese hamster ovary cells after activation of the metabotropic m1-muscarinic receptor. Fast application of acetylcholine onto the cells evoked a biphasic heat wave that was blocked by atropine, and after a brief delay was followed by a calcium wave. Atropine applied by itself produced a monophasic heat wave in the cells, suggesting that its interactions with the receptor activate some intracellular metabolic pathways. The thermal imaging technique introduced here should provide new insights into cellular functions by resolving the location, kinetics, and quantity of intracellular heat production.
authors.affiliation: Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-4124, USA. zohar@codon.nih.gov
authors.forename: O
authors.initials: O
authors.lastname: Zohar
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Shinagawa
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: D
authors.initials: D
authors.lastname: Elbaum
authors.forename: D L
authors.initials: DL
authors.lastname: Alkon
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002151:Calorimetry / Q000379:methods; D006224:Cricetinae; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013816:Thermodynamics
chemical_list: D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D001285:Atropine; D002118:Calcium