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

Abstract

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.

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

“…These features are characteristic for sodium current transmitted by the Na v 1.9 channels [6]. Expression of TTX-resistant channels (Na v 1.9 and Na v 1.8) and their activity (presence of TTX-resistant currents with different activation potentials) was already shown before in pyramidal neurons of the prefrontal cortex of rats [8][9][10]. Thus, our electrophysiological studies provide additional confirmation of the presence of functional, TTX-resistant channels with low activation potential in pyramidal cortex neurons of rats.…”

“…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.…”

Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β1-Adrenergic Receptors and HCN Channels

“…This residual current could have been due to an incomplete blockade of the HCN channels or another ionic conductance involved in the membrane potential control by β 1 -adrenergic receptors. Furthermore, this current may depend on activation of a TTX-resistant Na + current ( Kurowski et al, 2015 ; Gawlak et al, 2017 ; Radzicki et al, 2017 ) or inhibition of constitutively active K + currents ( Ładno et al, 2017 ).…”

Ionic Mechanism Underlying Rebound Depolarization in Medial Prefrontal Cortex Pyramidal Neurons

“…The experiments were performed on the neurons of 72 adult (58–62 days old) male Wistar rats obtained from a local animal facility. The applied experimental procedures were similar to those used in our recent studies (Kurowski et al, 2015 ; Szulczyk, 2016 ; Gawlak et al, 2017 ; Grzelka et al, 2017 ). Rats were decapitated, and their brains were removed and placed in cold (0–4°C) extracellular solution containing the following (in mM): 125 NaCl, 25 NaHCO 3 , 3 KCl, 1.25 NaH 2 PO 4 , 0.5 CaCl 2 , 6 MgCl 2 , and 25 glucose (bubbled with 95% O 2 /5% CO 2 ).…”

“…Recordings were obtained from pyramidal neurons located 600–800 μm from the cortical surface. This area of the mPFC corresponds to layer V pyramidal neurons in 58- to 62-day-old rats (Gawlak et al, 2017 ). The neurons were observed via differential interference contrast microscopy using a 40× water-immersion objective, a camera (C7500-51), and a camera controller (C2741-62) from Hamamatsu Photonics K.K.…”