Inward rectifier potassium channels interact with calcium channels to promote robust and physiological bistability

Anaëlle De Worm; Guillaume Drion; Pierre Sacré

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arXiv · 2411.14107

Inward rectifier potassium channels interact with calcium channels to promote robust and physiological bistability

Anaëlle De Worm·Guillaume Drion·Pierre Sacré

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Abstract

Projection neurons in the dorsal horn relay nociceptive input to supraspinal centers. During central sensitization, a subset of them switches from tonic firing to plateau potentials with sustained afterdischarges, a change that requires intrinsic bistability between a resting and a spiking state. Voltage-gated L-type calcium (CaL) channels can produce bistability, but reach physiological resting states only when paired with voltage-gated potassium channels, most of which simultaneously shrink the bistability window. How robust, physiological bistability arises has therefore remained unclear. Using a minimal conductance-based model, we show that inward rectifier potassium (Kir) channels enlarge the bistability window when combined with CaL channels, while M-type potassium (KM) channels slightly reduce it. Within the parameter region where bistability is both robust and physiological, both channel types can sustain bistability, but the CaL+Kir combination produces a substantially larger window and is more robust to noise and intrinsic variability. This window-enlarging effect traces to a shape feature of the outward Kir steady-state current: like the CaL current, it has a region of negative differential conductance around the spike threshold, a feature absent from KM and from most other voltage-gated potassium currents. Bifurcation analysis further shows that the two pairs support qualitatively distinct excitability: plateau-generating bistability for CaL+Kir and resonator-like dynamics for CaL+KM. These conclusions hold in a two-compartment model of deep projection neurons with realistic ion channel complements, and identify the CaL+Kir pair as a candidate intrinsic mechanism for central sensitization.

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Anaëlle De Worm, Guillaume Drion, Pierre Sacré. 2026-05-28. Inward rectifier potassium channels interact with calcium channels to promote robust and physiological bistability. https://arxiv.org/abs/2411.14107

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