Abstract
Here we show that positive modulators (CyPPA and NS309) of Ca2+-activated K+ channels of small (SK) and intermediate (IK) conductances in cerebellar neurons decrease glutamate-evoked Ca2+ entry into neurons independently on the presence of Mg2+ in extracellular media. An analysis of neuronal viability after long-term (240 min) glutamate treatments demonstrated neuroprotective action of CyPPA and NS309. Extracellular Mg2+ did not protect neurons from apoptosis during prolonged treatment with glutamate. Activation of SK and IK channels results in local membrane hyperpolarization, which enhances Mg2+ block of NMDA receptors and reduces activation of voltage-dependent Ca2+ channels, which can explain neuroprotection caused by CyPPA or NS309. The obtained results reveal an important role Ca2+-activated K+ channels of small and intermediate conductance in the regulation of Ca2+ entry into cerebellar neurons via NMDA receptors and voltage-gated Ca2+ channels.
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Original Russian Text © Yu.D. Stepanenko, T.V. Karelina, D.A. Sibarov, P.A. Abushik, S.M. Antonov, 2017, published in Biologicheskie Membrany, 2017, Vol. 34, No. 4, pp. 313–317.
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Stepanenko, Y.D., Karelina, T.V., Sibarov, D.A. et al. The mechanism of neuroprotection by positive modulation of Ca2+-activated K+ channels of cerebellar neurons in primary culture. Biochem. Moscow Suppl. Ser. A 11, 248–251 (2017). https://doi.org/10.1134/S1990747817030084
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DOI: https://doi.org/10.1134/S1990747817030084