In bone cells, an extracellular influx and intracellular release is rapidly activated by strain, pressure, and fluid flow. As such, it is a powerful second messenger important in proliferation, differentiation, mitosis, and motility. Calcium levels are maintained at very low concentrations intracellularly via its removal to the extracellular environment and sequestration in the endoplasmic reticulum. Intracellular calcium signaling regulates numerous basic cellular processes including proliferation, differentiation, and cellular motility. Jacobs, in Osteoporosis (Fourth Edition), 2013 Intracellular Calcium Signaling Because the function of intracellular calcium channels is modulated by interaction with regulatory molecules and proteins on both the luminal and the cytoplasmic side of the protein, the bilayer lipid membrane system offers unique opportunities to investigate the function of these channels. For example, all intracellular calcium channels are modulated by the luminal and cytosolic calcium concentration and therefore barium is often chosen as a current carrier not affecting channel function. The low ion selectivity of intracellular calcium channels also makes the use of current carriers possible that do not interfere with ion channel function. A buffer containing a low concentration of the divalent current carrier is present at the cytosolic side of the channel protein (termed the cis side of the bilayer lipid membrane). Typically a divalent current carrier in the several millimolar concentration range is chosen for the buffer on the luminal side of the channel protein (termed the trans side of the bilayer lipid membrane). Therefore, even if other intracellular channels such as potassium and chloride channels are present in membrane preparations of intracellular calcium channels, their contribution to ion channel currents measured in bilayer lipid membranes can be excluded by choosing the appropriate composition of buffers on either side of the bilayer lipid membrane. This is due to the fact that of the metal cations only calcium ions form a physiologically relevant electrochemical gradient across the membranes of sarcoplasmic reticulum, endoplasmic reticulum, Golgi apparatus and nuclear envelope, the expression sites of intracellular calcium channels. Intracellular calcium channels unlike their analogues of the plasma membrane, such as voltage and ligand gated calcium channels typically show a low selectivity for their current carrier calcium and conduct other divalent cations as well as monovalent cations. Koulen, in Membrane Science and Technology, 2003 1.2 Biophysical properties of intracellular calcium channels that make bilayer lipid membranes the method of choice for their analysis

Calcium 10.7