HCN channels promote Na/K‐ATPase activity during slow afterhyperpolarization after seizure‐like events in vitro DOI Open Access
Dmitry V. Amakhin,

D. S. Sinyak,

Elena B. Soboleva

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are strongly involved in the regulation of neuronal excitability, with their precise role being determined by subcellular localization and interaction other ion transporters. Their causing epileptic seizures is not fully understood. Using whole-cell patch-clamp recordings rat brain slices, we show that HCN constitute a substantial fraction membrane conductance deep entorhinal principal neurons. 4-aminopyridine model vitro, channel blockade ZD-7288 increases frequency seizure-like events (SLEs) alters time course afterhyperpolarization after SLEs (post-SLE AHP), promoting its faster onset making it more transient. Simultaneous K+ ion-selective electrode revealed changes potential extracellular concentration presence differed from control, which can be explained altered Na/K-ATPase [sodium-potassium adenosine triphosphatase (sodium-potassium pump)] activity SLEs. To confirm this hypothesis, demonstrated ouabain sensitivity post-SLE AHP showed loading neurons high intracellular Na+ prevented effect on AHP. Taken together, results obtained suggest during AHP, influx through helps to maintain hyperactivity, resulting longer pauses between Mathematical modelling confirmed feasibility proposed mechanism. Such an interplay may crucial for seizure termination epilepsy. KEY POINTS: significant resting modulate cortex. The reduces duration follows them. affect sodium dynamics, prolonging (sodium-potassium) pump] SLEs, turn

Language: Английский

HCN channels promote Na/K‐ATPase activity during slow afterhyperpolarization after seizure‐like events in vitro DOI Open Access
Dmitry V. Amakhin,

D. S. Sinyak,

Elena B. Soboleva

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are strongly involved in the regulation of neuronal excitability, with their precise role being determined by subcellular localization and interaction other ion transporters. Their causing epileptic seizures is not fully understood. Using whole-cell patch-clamp recordings rat brain slices, we show that HCN constitute a substantial fraction membrane conductance deep entorhinal principal neurons. 4-aminopyridine model vitro, channel blockade ZD-7288 increases frequency seizure-like events (SLEs) alters time course afterhyperpolarization after SLEs (post-SLE AHP), promoting its faster onset making it more transient. Simultaneous K+ ion-selective electrode revealed changes potential extracellular concentration presence differed from control, which can be explained altered Na/K-ATPase [sodium-potassium adenosine triphosphatase (sodium-potassium pump)] activity SLEs. To confirm this hypothesis, demonstrated ouabain sensitivity post-SLE AHP showed loading neurons high intracellular Na+ prevented effect on AHP. Taken together, results obtained suggest during AHP, influx through helps to maintain hyperactivity, resulting longer pauses between Mathematical modelling confirmed feasibility proposed mechanism. Such an interplay may crucial for seizure termination epilepsy. KEY POINTS: significant resting modulate cortex. The reduces duration follows them. affect sodium dynamics, prolonging (sodium-potassium) pump] SLEs, turn

Language: Английский

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