🔔Calcium Signaling
Calcium is one of the most versatile second messengers in biology. Its concentration in the cytosol is tightly controlled and can increase 10-100 fold during signaling, triggering diverse cellular responses from muscle contraction to gene expression.
📊 The Calcium Signal
100 nM
Resting [Ca²⁺]ᵢ
1-10 µM
Signaling [Ca²⁺]ᵢ
~10,000×
Gradient (out:in)
🔔Calcium Signaling Circuit Simulator
Calcium Levels
[Ca²⁺]cytosol:
0.10 µM
[Ca²⁺]ER:
500 µM
Calmodulin:
0% active
Note: Resting [Ca²⁺]ᵢ ≈ 100 nM (0.1 µM). Signaling raises it to 1-10 µM. ER stores calcium at ~500 µM (5000× higher than cytosol).
🚪Calcium Entry and Exit Pathways
| Protein | Location | Function | Regulation |
|---|---|---|---|
| VOCCs (L, T, N, P/Q) | Plasma membrane | Ca²⁺ entry on depolarization | Voltage |
| IP₃R | ER membrane | Ca²⁺ release from ER | IP₃ + Ca²⁺ |
| RyR | ER/SR membrane | Ca²⁺ release (CICR) | Ca²⁺ |
| SERCA | ER membrane | Ca²⁺ reuptake into ER | ATP, PLN |
| PMCA | Plasma membrane | Ca²⁺ extrusion | ATP, calmodulin |
| NCX | Plasma membrane | 3Na⁺/1Ca²⁺ exchange | Na⁺ gradient |
⚙️Calcium Effector Proteins
Calmodulin (CaM)
Kd: ~1 µM
Targets: CaMK, MLCK, calcineurin, nNOS
Kinase activation, smooth muscle contraction
Troponin C
Kd: ~1 µM
Targets: Troponin I/T complex
Skeletal/cardiac muscle contraction
PKC
Kd: ~0.5 µM
Targets: Many substrates
Cell proliferation, secretion
Synaptotagmin
Kd: ~20 µM
Targets: SNARE complex
Neurotransmitter release