[en] 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.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
De Worm, Anaëlle ; Université de Liège - ULiège > Montefiore Institute of Electrical Engineering and Computer Science
Drion, Guillaume ; Université de Liège - ULiège > Montefiore Institute of Electrical Engineering and Computer Science
Sacré, Pierre ; Université de Liège - ULiège > Montefiore Institute of Electrical Engineering and Computer Science
Language :
English
Title :
Inward rectifier potassium channels interact with calcium channels to promote robust and physiological bistability.
BELSPO - Belgian Federal Science Policy Office F.R.S.-FNRS - Fonds de la Recherche Scientifique Walloon Region
Funding text :
Funding: This work was supported by the Belgian Government through the Federal Public Service Policy and Support (NEMODEI2 to A.D.W., G.D., and P.S.). Computational resources have been provided (to A.D.W.) by the Consortium des \u00C9quipements de Calcul Intensif (C\u00C9CI), funded by the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under Grant No. 2.5020.11 and by the Walloon Region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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