Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons

Szulczyk, Bartłomiej; Nurowska, Ewa

doi:10.1016/j.bbrc.2017.07.109

Cited by 18 publications

(18 citation statements)

References 22 publications

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“…Two types of voltage‐dependent neuronal Na + currents, Nav1.8, and Nav1.9 TTX‐resistant currents, could be potentially evoked in our experimental conditions. Recently, the presence of Nav1.8‐like currents has been reported in cortical neurons (Szulczyk and Nurowska, ). Moreover, in our study, we demonstrated that Nav1.8 channel mRNA is present in mPFC tissue [see our Fig.…”

Section: Discussionmentioning

confidence: 97%

“…This lack of change facilitates the separation of the Nav1.9 current from the Nav1.8 current in cells expressing both channels (Cummins et al, ; Coste et al, ; Maruyama et al, ). To evaluate the activation kinetics, the mean current amplitude was measured 30–50 ms after voltage step onset, that is, when Nav1.8 channels are already time‐dependently inactivated (Szulczyk and Nurowska, ). To construct inactivation curves, currents were evoked by a voltage step of −40 mV, which does not activate Nav1.8 but is well above the threshold for the Nav1.9 current (Cummins et al, ; Coste et al, ; Maruyama et al, ; Szulczyk and Nurowska, ).…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the activation kinetics, the mean current amplitude was measured 30-50 ms after voltage step onset, that is, when Nav1.8 channels are already time-dependently inactivated . To construct inactivation curves, currents were evoked by a voltage step of 240 mV, which does not activate Nav1.8 but is well above the threshold for the Nav1.9 current (Cummins et al, 1999;Coste et al, 2004Coste et al, , 2007Maruyama et al, 2004;Szulczyk and Nurowska, 2017). mPFC pyramidal neurons have frequently been shown to exhibit persistent, low-threshold, and TTXsensitive Na 1 currents (Gorelova and Yang, 2000;Maurice et al, 2001;Astman et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

Gawlak

Szulczyk

Berłowski

et al. 2017

Developmental Neurobiology

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Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20-day old), late adolescent (60-day old), and adult (6- to 7-month old) rats. First, we demonstrated that layer II and V mPFC pyramidal neurons in slices obtained from young rats exhibited a TTX-resistant, low-threshold, noninactivating, and voltage-dependent Na current. The mRNA expression of the SCN11a gene (which encodes the Nav1.9 channel) in mPFC tissue was significantly higher in young rats than in late adolescent and adult rats. Nav1.9 protein was immunofluorescently labeled in mPFC cells in slices and analyzed via confocal microscopy. Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371-1384, 2017.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

Gawlak

Szulczyk

Berłowski

et al. 2017

Developmental Neurobiology

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“…In the veratrine test, both carbamazepine and valproate reduced the licking time after subcutaneous injection of veratrine into the paw. Previous reports have shown that not only TTX‐S sodium channels molecules but also TTX‐R sodium channels molecules are influenced by carbamazepine (Song et al, ) and valproate (Szulczyk & Nurowska, ). These results suggest that VGSCs play a crucial role in the analgesic effects of these drugs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the antinociceptive activities of several sodium channel blockers using veratrine test in mice

Yoshizawa

Arai

Suzuki

et al. 2018

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An important role of voltage-gated sodium channels (VGSCs) in many different pain states has been established in animal models and humans wherein sodium channel blockers partially ameliorate pain. However, behavioral tests for screening analgesics that exhibit pharmacologic action by acting on VGSCs are rarely reported, and there are no studies on antinociception using veratrine as a nociceptive agent. The aim of the present study was to examine the amount of nociceptive behavior evoked by subcutaneous administration of veratrine into the hind paw and investigate whether veratrine can be used as a VGSC agonist to test the pharmacological properties of candidate analgesics via sodium channel blockade. We report for the first time that intraplantar injection of veratrine produced a reproducible nociceptive response in mice. Furthermore, several sodium channel blockers, namely carbamazepine, valproate, mexiletine, and the selective Nav1.7 inhibitor PF-04856264, but not flecainide or pilsicainide, reduced veratrine-induced nociception. In contrast, calcium channel blockers gabapentin and ethosuximide did not change veratrine-induced nociception. The veratrine test in mice might be a useful tool, at least in part, to evaluate the potential analgesic effect of sodium channel blockers.

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“…It was accepted until recently that Na v 1.9 channels are absent in the central nervous system [7], however, the presence of the Na v 1.9 protein was proven in pyramidal neurons of the V layer of prefrontal cortex in rats using confocal microscopy and Na v 1.9 antibody labelling [8,9]. Previous studies showed that TTX-resistant sodium current in pyramidal neurons of rat cortex displays characteristics typical for Nav1.8 and Nav1.9 channels [9,10]. Thus, depending on the patch clamp protocol used, it may be a result of currents from both these channels.…”

Section: Introductionmentioning

confidence: 99%

TTX-resistant sodium currents in medial prefrontal cortex pyramidal neurons depend on extracellular Ca2+ concentration

Sławińska

Nurowska

Dworakowska

2019

Medical Research Journal

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Background: Previous reports reported the presence of TTX-resistant Nav1.8 and Nav1.9 sodium channels in the cortex pyramidal neurons. A characteristic feature of Nav1.9 channels is activation at voltages close to -70 mV. Therefore, they do not participate directly in the action potential but contribute to the regulation of the resting membrane potential. Their physiological role is modulation of cell excitability.The aim of the study was to investigate, with the use of patch clamp technique, the dependence of the activation thresholds of TTX-resistant sodium currents on the concentration of extracellular calcium in medial prefrontal cortex pyramidal neurons in rats. Results:The recorded values of the threshold of the voltage-dependent sodium currents were in the range of -65 mV to -75 mV. This suggests that the sodium currents may result from the presence of Nav1.9 channels in the rat pyramidal neurons. The threshold for the activation of sodium currents depended on the concentration of Ca 2+ . Increasing the concentration of calcium ions in the extracellular solution by 5 mM caused the depolarizing shift in the activation potential by about 10 mV. The effect of calcium ion concentration on the potential of TTX-resistant currents activation suggests that Nav1.9 channels are modulated by extracellular Ca 2+ concentration. Conclusions:The study has experimentally confirmed that TTX-resistant channels are present in the cell membrane of the rat prefrontal cortex pyramidal neurons and may, therefore, take a physiological role in the conductivity of sodium currents in a manner dependent on the concentration of extracellular ions.

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Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons

Cited by 18 publications

References 22 publications

Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

Evaluation of the antinociceptive activities of several sodium channel blockers using veratrine test in mice

TTX-resistant sodium currents in medial prefrontal cortex pyramidal neurons depend on extracellular Ca2+ concentration

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