Changes in enthalpy (i.e., heat content) occur during the diverse intr
acellular chemical and biophysical interactions that take place in the
life cycle of biological cells. Such changes have previously been mea
sured for cell suspensions or cell-free biochemical extracts by using
microcalorimetry, thermocouples, or pyroelectric films, all of which a
fford minimal spatial or temporal resolution. Here we present a novel
thermal imaging method that combines both diffraction-limited spatial
(similar to 300 nm) and sampling-rate-limited time resolution, using t
he temperature-dependent phosphorescence intensity of the rare earth c
helate Eu-TTA (europium (III) thenoyltrifluoro-acetonate). With this t
hermosensitive dye, we imaged intracellular heat waves evoked in Chine
se hamster ovary cells after activation of the metabotropic ml-muscari
nic receptor, Past application of acetylcholine onto the cells evoked
a biphasic heat wave that was blocked by atropine, and after a brief d
elay was followed by a calcium wave. Atropine applied by itself produc
ed a monophasic heat wave in the cells, suggesting that its interactio
ns with the receptor activate some intracellular metabolic pathways. T
he thermal imaging technique introduced here should provide new insigh
ts into cellular functions by resolving the location, kinetics, and qu
antity of intracellular heat production.