Molecular and functional profiling of histamine receptor-mediated calcium ion signals in different cell lines

Calcium ions (Ca2+) play a pivotal role in cellular physiology. Often Ca2+-dependent processes are studied in commonly available cell lines. To induce Ca2+ signals on demand, cells may need to be equipped with additional proteins. A prominent group of membrane proteins evoking Ca2+ signals are G-protein coupled receptors (GPCRs). These proteins register external signals such as photons, odorants, and neurotransmitters and convey ligand recognition into cellular responses, one of which is Ca2+ signaling. To avoid receptor cross-talk or cross-activation with introduced proteins, the repertoire of cell-endogenous receptors must be known. Here we examined the presence of histamine receptors in six cell lines frequently used as hosts to study cellular signaling processes. In a concentration-dependent manner, histamine caused a rise in intracellular Ca2+ in HeLa, HEK 293, and COS-1 cells. The concentration for half-maximal activation (EC50) was in the low micromolar range. In individual cells, transient Ca2+ signals and Ca2+ oscillations were uncovered. The results show that (i) HeLa, HEK 293, and COS-1 cells express sufficient amounts of endogenous receptors to study cellular Ca2+ signaling processes directly and (ii) these cell lines are suitable for calibrating Ca2+ biosensors in situ based on histamine receptor evoked responses.