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Inward rectifier potassium channels interact with calcium channels to promote robust and physiological bistability
De Worm Anaëlle1, Drion Guillaume1, Sacré Pierre1
1Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.
Plos Computational Biology
|July 28, 2026
Summary
Inward rectifier potassium (Kir) channels, when paired with L-type calcium (CaL) channels, create robust neuronal bistability, crucial for central sensitization. This CaL+Kir combination offers greater stability than CaL+M-type potassium (KM) channels.
Area of Science:
- Computational Neuroscience
- Ion Channel Physiology
- Pain Signaling
Background:
- Projection neurons in the dorsal horn transmit pain signals.
- Central sensitization involves a shift in neuronal firing patterns.
- Neuronal bistability is essential for this firing pattern shift.
Purpose of the Study:
- To investigate how robust, physiological neuronal bistability arises.
- To determine the roles of L-type calcium (CaL) and specific potassium channels in bistability.
- To identify mechanisms underlying central sensitization in dorsal horn neurons.
Main Methods:
- Development of a minimal conductance-based computational model.
- Analysis of voltage-gated L-type calcium (CaL) channels paired with inward rectifier potassium (Kir) and M-type potassium (KM) channels.
- Bifurcation analysis and simulation in a two-compartment model of deep projection neurons.
Main Results:
- Inward rectifier potassium (Kir) channels enlarge the bistability window when paired with CaL channels.
- The CaL+Kir combination yields more robust and stable bistability compared to CaL+KM.
- The CaL+Kir pair exhibits unique negative differential conductance contributing to plateau potentials.
Conclusions:
- The CaL+Kir channel combination provides a robust mechanism for physiological neuronal bistability.
- This bistability is a key intrinsic property enabling central sensitization.
- The CaL+Kir pair is identified as a potential intrinsic mechanism driving central sensitization.
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