Forschung

The cytosolic free Ca²⁺ concentration ([Ca²⁺]_cytosol) is typically 50-150 nM in most mammalian cells, while intracellular Ca²⁺ stores such as the endoplasmic reticulum (ER) contain free Ca²⁺ concentrations ([Ca²⁺]_ER) in the range of 100-800 µM at rest. The extracellular Ca²⁺ concentration is 2.0-2.5 mM in most tissues. Accordingly, the Ca²⁺ concentration gradient amounts approximately 30000 across the plasma membrane and varies between 666 and 16000 across the ER membrane. Upon stimulation, these Ca²⁺ concentration gradients determine the Ca²⁺ fluxes across cell membranes. As illustrated for the effects of thapsigargin (TG), more than a 7-fold increase of cytosolic Ca²⁺ is produced by the release of small amounts of Ca²⁺ from ER. Strong clearance mechanisms remove Ca²⁺ efficiently from cytosol in the absence of external Ca²⁺ (zero ext. Ca²⁺) and sustained Ca²⁺ entry is seen in the presence of external Ca²⁺ (2 mM Ca²⁺).

Our research group investigates central aspects of the Ca²⁺ homeostasis in mammalian cells. Specifically, we study the function and regulation of ion channels localized in the plasma membrane such as voltage-dependent Ca²⁺ channels (VDCC). ORAI channels that allow the so-called store-operated Ca²⁺ entry (SOCE) and transient receptor potential (TRP) channels, which can also support Ca²⁺ entry and modulate the membrane potential, are also in focus of our research projects. Recently, we showed that the translocon, which is formed by Sec61 complexes in the ER membrane, supports Ca²⁺ fluxes into the cytosol. Other central players in the Ca²⁺ homeostasis of mammalian cells are ER resident Ca²⁺ pumps (SERCA) as well as ryanodine and IP3 receptors.