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.