Analytical studies of rapidly inactivating and noninactivating sodium currents in differentiated NG108-15 neuronal cells

Sheng-Nan Wu, Bing Shuo Chen, Tai I. Hsu, Hsung Peng, Yung Han Wu, Yi Ching Lo

Research output: Contribution to journalArticle

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Abstract

The rapidly inactivating (INaf) and noninactivating Na+ currents (INa(NI)) were characterized in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP in this study. Standard activation and inactivation protocols were used to evaluate the steady-state and kinetic properties of the INaf present in these cells. The voltage protocols with a slowly depolarizing ramp were implemented to examine the properties of INa(NI). Based on experimental data and computer simulations, a window component of the rapidly inactivating sodium current (INaf(W)) was also generated in response to the slowly depolarizing ramp. The INaf(W) was subtracted from INa(NI) to yield the persistent Na+ current (INa(P)). Our results demonstrate the presence of INa(P) in these cells. In addition to modifying the steady-state inactivation of INaf, ranolazine or riluzloe could be effective in blocking INaf(W) and INa(P). The ability of ranolazine and riluzole to suppress INa(P) was greater than their ability to inhibit INaf(W). In current-clamp recordings, current-induced voltage oscillations were applied to elicit action potentials (APs) through a gradual transition between spontaneous depolarization and upstroke. Ranolazine or riluzole at a concentration of 3 μM then effectively suppressed the AP firing generated by oscillatory changes in membrane current. The data suggest that a small rise in INa(NI) facilitates neuronal hyper-excitability due the decreased threshold of AP initiation. The underlying mechanism of the inhibitory actions of ranolazine or riluzole on membrane potential in neurons or neuroendocrine cells in vivo may thus be associated with their blocking of INa(NI).

Original languageEnglish
Pages (from-to)828-836
Number of pages9
JournalJournal of Theoretical Biology
Volume259
Issue number4
DOIs
Publication statusPublished - 2009 Aug 21

Fingerprint

Riluzole
action potentials
Sodium
neurons
sodium
Action Potentials
Membranes
Architectural Accessibility
Cell
Induced currents
inactivation
Depolarization
Clamping devices
Electric potential
Action Potential
Neurons
Chemical activation
cyclic AMP
cells
membrane potential

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Wu, Sheng-Nan ; Chen, Bing Shuo ; Hsu, Tai I. ; Peng, Hsung ; Wu, Yung Han ; Lo, Yi Ching. / Analytical studies of rapidly inactivating and noninactivating sodium currents in differentiated NG108-15 neuronal cells. In: Journal of Theoretical Biology. 2009 ; Vol. 259, No. 4. pp. 828-836.
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abstract = "The rapidly inactivating (INaf) and noninactivating Na+ currents (INa(NI)) were characterized in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP in this study. Standard activation and inactivation protocols were used to evaluate the steady-state and kinetic properties of the INaf present in these cells. The voltage protocols with a slowly depolarizing ramp were implemented to examine the properties of INa(NI). Based on experimental data and computer simulations, a window component of the rapidly inactivating sodium current (INaf(W)) was also generated in response to the slowly depolarizing ramp. The INaf(W) was subtracted from INa(NI) to yield the persistent Na+ current (INa(P)). Our results demonstrate the presence of INa(P) in these cells. In addition to modifying the steady-state inactivation of INaf, ranolazine or riluzloe could be effective in blocking INaf(W) and INa(P). The ability of ranolazine and riluzole to suppress INa(P) was greater than their ability to inhibit INaf(W). In current-clamp recordings, current-induced voltage oscillations were applied to elicit action potentials (APs) through a gradual transition between spontaneous depolarization and upstroke. Ranolazine or riluzole at a concentration of 3 μM then effectively suppressed the AP firing generated by oscillatory changes in membrane current. The data suggest that a small rise in INa(NI) facilitates neuronal hyper-excitability due the decreased threshold of AP initiation. The underlying mechanism of the inhibitory actions of ranolazine or riluzole on membrane potential in neurons or neuroendocrine cells in vivo may thus be associated with their blocking of INa(NI).",
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Analytical studies of rapidly inactivating and noninactivating sodium currents in differentiated NG108-15 neuronal cells. / Wu, Sheng-Nan; Chen, Bing Shuo; Hsu, Tai I.; Peng, Hsung; Wu, Yung Han; Lo, Yi Ching.

In: Journal of Theoretical Biology, Vol. 259, No. 4, 21.08.2009, p. 828-836.

Research output: Contribution to journalArticle

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AU - Chen, Bing Shuo

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AU - Wu, Yung Han

AU - Lo, Yi Ching

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AB - The rapidly inactivating (INaf) and noninactivating Na+ currents (INa(NI)) were characterized in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP in this study. Standard activation and inactivation protocols were used to evaluate the steady-state and kinetic properties of the INaf present in these cells. The voltage protocols with a slowly depolarizing ramp were implemented to examine the properties of INa(NI). Based on experimental data and computer simulations, a window component of the rapidly inactivating sodium current (INaf(W)) was also generated in response to the slowly depolarizing ramp. The INaf(W) was subtracted from INa(NI) to yield the persistent Na+ current (INa(P)). Our results demonstrate the presence of INa(P) in these cells. In addition to modifying the steady-state inactivation of INaf, ranolazine or riluzloe could be effective in blocking INaf(W) and INa(P). The ability of ranolazine and riluzole to suppress INa(P) was greater than their ability to inhibit INaf(W). In current-clamp recordings, current-induced voltage oscillations were applied to elicit action potentials (APs) through a gradual transition between spontaneous depolarization and upstroke. Ranolazine or riluzole at a concentration of 3 μM then effectively suppressed the AP firing generated by oscillatory changes in membrane current. The data suggest that a small rise in INa(NI) facilitates neuronal hyper-excitability due the decreased threshold of AP initiation. The underlying mechanism of the inhibitory actions of ranolazine or riluzole on membrane potential in neurons or neuroendocrine cells in vivo may thus be associated with their blocking of INa(NI).

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