The provided code is a computational model of the electrical activity in pituitary corticotroph cells, specifically exploring how chronic stress facilitates bursting electrical activity in these cells. Here, we focus on the biological basis that the code is modeling with connections to relevant physiological and cellular functions.
Pituitary corticotroph cells are endocrine cells located in the anterior pituitary gland. They play a crucial role in the body's response to stress by secreting adrenocorticotropic hormone (ACTH) in response to Corticotropin-Releasing Hormone (CRH) from the hypothalamus. The code models the electrical activity of these cells under different conditions, particularly in the presence or absence of CRH, a stress-related hormone.
The model revolves around various types of ionic currents that influence the membrane potential of the corticotrophs. These ionic currents are central to the electrical activity modeling in the cells:
L-type Calcium Channels (vca): These channels allow calcium ions to enter the cell, which is crucial for triggering cellular activities, including hormone secretion. The code models the opening and closing of these channels based on membrane potential and CRH presence.
Delayed Rectifier Potassium Channels (vk): These channels help repolarize the cell membrane after depolarization, crucial for rhythmic electrical activity and maintaining membrane potential stability.
Inward Rectifier Potassium Channels (ikir): These channels stabilize resting membrane potential and modulate membrane excitability.
BK Channels (Big Potassium Channels): Separate units for BK-STREX and BK-ZERO variants are modeled. These calcium-sensitive potassium channels play a significant role in shaping action potentials and neuronal firing patterns.
Leak and Non-selective Channels: These channels contribute to the resting potential and help regulate cell excitability.
The model incorporates various gating variables and dynamic equations to simulate the opening and closing of ion channels:
Voltage-Dependent Gating: Channels open or close in response to changes in membrane potential, characterized by their Nernst potentials and half-activation voltages.
Calcium Dynamics: The concentration of intracellular calcium ions affects the activity of certain channels, integrating both electrophysiological activity and cellular signaling.
Stochastic Elements: Some channels, particularly the BK-STREX and BK-ZERO, involve stochastic elements reflecting biological variability in channel opening and closing. The model uses binomial trials and random selection to simulate variability and interactions with inhibitors like paxilline.
CRH: The presence or absence of CRH modulates the total number and activity of specific ion channels (e.g., BK-STREX and BK-ZERO) and thereby influences the electrical behavior of corticotrophs under stress.
Paxilline: This is a BK channel inhibitor, and its effect is modeled to investigate how blocking certain BK channels alters the electrical activity, reflecting potential pharmacological interventions.
Overall, the code provides a nuanced simulation of how ionic currents and channel dynamics contribute to the electrical behavior of pituitary corticotrophs under varying conditions of stress and pharmacological intervention. By integrating electrophysiological and stochastic processes, the model mimics the complex interplay of factors governing hormone release in stress response pathways.