IMPLICATIONS OF Kv7 INHIBITORS AND ACTIVATORS OF POTASSIUM CHANNELS ON THE STRUCTURE OF PAROXYSISMAL DEPOLYARISATION SHIFT CLASTERS IN EPILEPTIFORM ACTIVITY
DOI:
https://doi.org/10.34689/sfag2n96Keywords:
inhibitory neurons, action potential, potential-dependent calcium channels, spontaneous synchronous activity, AMPA receptor, hyperexcitation, epilepsy, potential-dependent potassium channels Kv7Abstract
Relevance: Seizures of epilepsy are a consequence of a weakening of the inhibitory GABAergic system and, due to the
presence of positive feedback, can lead to the death of neurons. The complexity of epilepsy treatment is due to the
complexity of the process in which the expression of more than 1,000 genes changes. The presence of cellular models of
epileptiform activity somewhat simplifies the task of investigating the nature of the phenomenon and allows us to establish
the role of many participants in the process, and to build a chain of signal transmission with their participation and to find out
the mechanisms of regulation of their activity. The discovery of the involvement of potential-dependent potassium channels
(Kv7) and calcium-permeable AMP receptors in epileptiform activity is a definite step in this direction and opens up new ways
of pharmacological correction of hyperexcitation.
Aim: To study the effect of Kv7 channel inhibitors and activators on the structure of clusters of paroxysmal depolarization
shift (PDS) in epileptiform activity.
Materials and methods: The experiments used a mixed neuroglial culture of hippocampal cells (12-14 DIV) isolated
from the brain of newborn (1-3 days old) Wistar rats. All studies were conducted at the cellular level in vitro. Changes in
intracellular calcium concentration were recorded using fluorescence microscopy. The Patch-Clamp method in the whole-cell
configuration was used to register changes in the membrane potential. The analysis and processing of the obtained results
was carried out using the Origin 9.1 and Image J programs.
Results and discussion: The experiments show that the cluster duration is discrete (varies by an integer number of
PDS) and varies in the control by one PDS, indicating that a stochastic process is involved in cluster induction. Kv7 channels
are involved in both cluster formation and the PDSs themselves.
Conclusion: Kv7 family potassium channels decrease the duration of action potential bursts and the duration of calcium
pulses during epileptiform activity, increasing the rate of posthyperpolarisation of the PDS cluster. Also direct activators and
inhibitors of Kv7 channels change such parameters of synchronous bundle activity and Ca2+ impulses as their duration,
amplitude, but not the frequency of depolarisation shifts in neurons during epileptiform activity.
References
Тулеуханов С.Т., Зинченко В.П., Қайрат Б.Қ., Тусупбекова Г.А., Малибаева А.Е. Эпилепсиялық белсенділік кезінде пароксизмальды деполяризациялық ығысу кластерлерінің құрылымына Kv7 тұқымдас калий каналдарының ингибиторлары мен активаторларының әсерін зерттеу // Ғылым және Денсаулық сақтау. 2025. Vol.27 (1), Б. 32-39. doi 10.34689/SH.20254.27.1.004
Tuleukhanov S.Т., Zinchenko V.P., Kairat B.K., Tussupbekova G.А., Malibayeva А.Е. Implications of Kv7 inhibitors and activators of potassium channels on the structure of paroxysismal depolyarisation shift clasters in epileptiform activity // Nauka i Zdravookhranenie [Science & Healthcare]. 2025. Vol.27 (1), pp. 32-39. doi 10.34689/SH.2025.27.1.004
Тулеуханов С.Т., Зинченко В.П., Қайрат Б.Қ., Тусупбекова Г.А., Малибаева А.Е. исследование влияния ингибиторов и активаторов калиевых каналов семейства Kv7 на структуру кластеров пароксизмального деполяризационного сдвига при эпилептиформной активности // Наука и Здравоохранение. 2025. Vol.27 (1), С.32-39. doi 10.34689/SH.2025.27.1.004
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