The code provided models the dynamics of intracellular calcium signaling through inositol trisphosphate receptors (IP3R) located on the endoplasmic reticulum (ER) membrane. Here's a breakdown of the biological basis behind the model: ### Biological Background 1. **Calcium Signaling**: - Calcium ions (Ca²⁺) are crucial secondary messengers in cellular signaling processes, influencing various cellular functions such as muscle contraction, neurotransmitter release, and gene expression. - The regulation and release of Ca²⁺ from intracellular stores, like the ER, are tightly controlled processes involving multiple pathways and proteins. 2. **Inositol Trisphosphate Receptors (IP3R)**: - IP3Rs are membrane channels located on the ER that release Ca²⁺ into the cytosol in response to inositol trisphosphate (IP3), which is generated upon specific external stimuli. - The density of IP3Rs on the ER surface affects the rate and magnitude of Ca²⁺ release. 3. **Model Components**: - The model describes a section of the cell with specified regions (ROIs) representing nodes. Each node contains a subset of cytosolic and ER geometries. - Calcium and IP3 concentrations and IP3R channel states are simulated within these nodes. 4. **Geometry and Stimulation**: - The mesh geometry represents different cellular compartments, including cytosol and ER, marked by tetrahedra and triangles. - The model introduces periodic stimuli in the form of IP3 infusions into specified nodes, mimicking physiological or experimental stimulation protocols. 5. **Calcium Indicator (GCaMP6s)**: - GCaMP6s, a genetically encoded calcium indicator, is modeled to track Ca²⁺ levels by forming a complex with calcium, enabling the detection of calcium fluctuations. 6. **Biological Dynamics**: - The model simulates calcium dynamics through time, where stochasticity in receptor activation and calcium diffusion are governed by probabilistic rules set within the simulation framework. - The "proba_fail" variable introduces variability in IP3 delivery, simulating the inefficiency or stochastic nature of biological signaling events. ### Key Aspects of Code Related to Biology - **IP3 and Calcium Dynamics**: The simulation involves changing levels of IP3 and Ca²⁺ within defined regions of the cell over time, influenced by IP3R activity on the ER membrane. - **Spatial Domains**: The use of tetrahedra and triangular elements to define precise spatial regions allows the code to model localized signaling events accurately, reflecting biological compartmentalization. - **Repeated Stimulation Protocols**: Mimics periodic calcium signaling pathways seen in various physiological contexts, providing insight into the temporal aspects of cellular signaling. This code, as part of a broader computational model, aims to help understand the spatial-temporal dynamics of calcium signaling and the role of IP3Rs in controlling calcium release from the ER under non-deterministic conditions.