Degeneracy in Astrocytic Potassium Buffering: A Minimal Model Capturing the Interplay Between Local and Long-Range Mechanisms

Abstract

Maintaining extracellular potassium (K+) homeostasis is critical for neuronal function, and astrocytes achieve this through a combination of local uptake and long-range spatial buffering. While degeneracy--the ability of different mechanisms to achieve the same function--is a fundamental property of biological systems, its role in astrocytic potassium buffering has remained unexplored. We present a minimal mathematical model that identifies essential buffering mechanisms while ensuring tractability and interpretability. Incorporating Kir channels and gap junction coupling, the model reproduces experimentally observed astrocyte membrane dynamics under various pharmacological conditions Parameter exploration reveals two levels of degeneracy. At the single-cell level, multiple parameter configurations yield similar membrane potential dynamics, indicating flexibility in local and spatial buffering contributions. At the functional level, despite variations in astrocyte morphology and buffering efficiency, homeostasis of extracellular K+ is restored, demonstrating homeostatic degeneracy. These findings highlight the robustness of astrocytic potassium regulation, showing that diverse buffering strategies ensure stability. Our work establishes a theoretical framework for understanding how astrocytic heterogeneity contributes to robust ionic homeostasis and offers perspectives for studying pathological conditions where buffering mechanisms are impaired.