Where is the Ca2+ concentration lower?

• A. Lower inside the cell
• B. Lower outside the cell
• C. Equal inside and outside
• D. Higher inside the cell

Answer: (A)

Ca2+ is kept at a very low free concentration inside the cell, while it is much higher outside the cell. This steep gradient is actively maintained by pumps and exchangers (such as PMCA and SERCA) and buffering within the cytosol and stores like the endoplasmic/sarcoplasmic reticulum. Because of this, the resting intracellular Ca2+ concentration is about 100 nanomolar, whereas extracellular Ca2+ is about 1–2 millimolar. Thus, the Ca2+ concentration is lower inside the cell. If it were lower outside, there would be little driving force for Ca2+ entry; if it were equal, there’d be no gradient; if it were higher inside, cytosolic Ca2+ would be abnormally elevated and disrupt signaling.