iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://pubmed.ncbi.nlm.nih.gov/30362397
Effects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3 - PubMed Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018;12(1):367-377.
doi: 10.1080/19336950.2018.1539611.

Effects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3

Mohammad-Reza Ghovanloo  1 , Colin H Peters  1 , Peter C Ruben  1
Affiliations

Effects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3

Mohammad-Reza Ghovanloo et al. Channels (Austin). 2018.

Abstract

Voltage-gated sodium channels are key contributors to membrane excitability. These channels are expressed in a tissue-specific manner. Mutations and modulation of these channels underlie various physiological and pathophysiological manifestations. The effects of changes in extracellular pH on channel gating have been studied on several sodium channel subtypes. Among these, Nav1.5 is the most pH-sensitive channel, with Nav1.2 and Nav1.4 being mostly pH-resistant channels. However, pH effects have not been characterized on other sodium channel subtypes. In this study, we sought to determine whether Nav1.1 and Nav1.3 display resistance or sensitivity to changes in extracellular pH. These two sodium channel subtypes are predominantly found in inhibitory neurons. The expression of these channels highly depends on age and the developmental stage of neurons, with Nav1.3 being found mostly in neonatal neurons, and Nav1.1 being found in adult neurons. Our present results indicate that, during extracellular acidosis, both channels show a depolarization in the voltage-dependence of activation and moderate reduction in current density. Voltage-dependence of steady-state fast inactivation and recovery from fast inactivation were unchanged. We conclude that Nav1.1 and Nav1.3 have similar pH-sensitivities.

Keywords: Acidosis; Nav1.1; Nav1.3; electrophysiology; pH.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Normalized conductance plotted against membrane potential. (a-b) Show overlaps of Nav1.1 and Nav1.3 conductance at pH6.4 and 7.4. The inset in panel (a) shows voltage protocol used. (c-d) Normalized current and voltage relationships.
Figure 2.
Figure 2.
Current density measured in pA/pF. (a) Sample macroscopic sodium currents elicited by depolarizations between −100 and + 80 mV. The inset in panel (a) shows voltage protocol used. (b) Average current (Y-axis) density of Nav1.1 and Nav1.3 at extracellular pH between 6.4 and 7.4.
Figure 3.
Figure 3.
Voltage-dependence of steady-state fast inactivation as normalized current plotted against membrane potential. (a) Show the voltage-dependence of fast inactivation of Nav1.1 at pH6.4 and pH7.4. The inset shows voltage protocol used. (b) Inactivating current traces associated with Nav1.1 in pH6.4 and pH7.4. (c) Show the voltage-dependence of fast inactivation of Nav1.3 at pH6.4 and pH7.4. (d) Inactivating current traces associated with Nav1.3 in pH6.4 and pH7.4.
Figure 4.
Figure 4.
Open-state fast inactivation time constants. (a-b) Time constants at −20, 0 and + 10 mV from Nav1.1 and Nav1.3 at pH6.4 and pH7.4. The inset in (a) shows the voltage protocol that was used.
Figure 5.
Figure 5.
Recovery from fast inactivation. (a-b) Show the normalized current is plotted against a range of recovery durations (s). The inset in (a) shows the pulse protocol that was used.
Figure 6.
Figure 6.
Action potential model. (a-b) Threshold level action potential simulation of Nav1.1 and Nav1.3 at pH7.4 and pH6.4. (c-d) Action potential simulations at increasing and sustained current injection intensities.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Catterall WA. Voltage-gated sodium channels at 60: structure, function and pathophysiology. J Physiol [Internet]. 2012. [cited 2017 June 3];590:2577–2589. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22473783 - PMC - PubMed
    1. Ghovanloo M-R, Aimar K, Ghadiry-Tavi R, et al. Physiology and pathophysiology of sodium channel inactivation [Internet] In: Robert J. French, Sergei Yu. Noskov, editors. Current topics in membranes. Amsterdam, Netherlands: Elsevier; 2016. 479–509. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1063582316300011 - PubMed
    1. Calhoun JD, Isom LL.. The role of non-pore-forming β subunits in physiology and pathophysiology of voltage-gated sodium channels In: Peter C. Ruben, editor. Voltage gated sodium channels. New York (NY): Springer; 2014. - PubMed
    1. Estacion M, Gasser A, Dib-Hajj SD, et al. A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons. Exp Neurol. 2010;224:362–368. - PubMed
    1. Cannon SC. Pathomechanisms in channelopathies of skeletal muscle and brain. Annu Rev Neurosci [Internet]. 2006;29:387–415. - PubMed

Publication types

Substances

Grants and funding

This work was supported by: Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (PCR); Mitacs Accelerate Grant (M-RG).