Citation: Feher, A.; Pócsi, M.; Papp,
F.; Szanto, T.G.; Csoti, A.; Fejes, Z.;
Nagy, B., Jr.; Nemes, B.; Varga, Z.
Functional Voltage-Gated Sodium
Channels Are Present in the Human
B Cell Membrane. Cells 2022, 11, 1225.
https://doi.org/10.3390/
cells11071225
Academic Editor: Rajesh Khanna
Received: 4 March 2022
Accepted: 3 April 2022
Published: 5 April 2022
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cells
Article
Functional Voltage-Gated Sodium Channels Are Present in the
Human B Cell Membrane
Adam Feher
1
, Marianna Pócsi
2
, Ferenc Papp
1
, Tibor G. Szanto
1
, Agota Csoti
1
, Zsolt Fejes
2
,
Béla Nagy, Jr.
2
, Balázs Nemes
3
and Zoltan Varga
1,
*
1
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen,
H-4032 Debrecen, Hungary; feher.adam@med.unideb.hu (A.F.); papp.ferenc@med.unideb.hu (F.P.);
szantogt80@gmail.com (T.G.S.); jelena45@gmail.com (A.C.)
2
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen,
H-4032 Debrecen, Hungary; pmarcsi89@gmail.com (M.P.); fejes.zsolt@med.unideb.hu (Z.F.);
nagy.bela@med.unideb.hu (B.N.J.)
3
Department of Organ Transplantation, Faculty of Medicine, Institute of Surgery, University of Debrecen,
H-4032 Debrecen, Hungary; nemes.balazs@med.unideb.hu
* Correspondence: veze@med.unideb.hu
Abstract: B cells express various ion channels, but the presence of voltage-gated sodium (Na
V
)
channels has not been confirmed in the plasma membrane yet. In this study, we have identified
several Na
V
channels, which are expressed in the human B cell membrane, by electrophysiological
and molecular biology methods. The sensitivity of the detected sodium current to tetrodotoxin was
between the values published for TTX-sensitive and TTX-insensitive channels, which suggests the
co-existence of multiple Na
V
1 subtypes in the B cell membrane. This was confirmed by RT-qPCR
results, which showed high expression of TTX-sensitive channels along with the lower expression
of TTX-insensitive Na
V
1 channels. The biophysical characteristics of the currents also supported
the expression of multiple Na
V
channels. In addition, we investigated the potential functional role
of Na
V
channels by membrane potential measurements. Removal of Na
+
from the extracellular
solution caused a reversible hyperpolarization, supporting the role of Na
V
channels in shaping and
maintaining the resting membrane potential. As this study was mainly limited to electrophysiological
properties, we cannot exclude the possible non-canonical functions of these channels. This work
concludes that the presence of voltage-gated sodium channels in the plasma membrane of human B
cells should be recognized and accounted for in the future.
Keywords: B cell; lymphocytes; voltage-gated sodium channel; patch-clamp electrophysiology;
tetrodotoxin
1. Introduction
Voltage-gated Na+ (Na
V
) channels are best known for initiating action potentials by
depolarizing the membrane of excitable cells. Na
V
1.1–1.9 are the nine members of this
family [1,2], of which Na
V
1.1–1.3 and 1.6 are mostly expressed in the neurons of the central
nervous system but can also be found in peripheral neurons, while Na
V
1.7–1.9 channels
are almost exclusively found in the peripheral neurons. Na
V
1.4 is the main Na
V
channel of
skeletal muscles, while Na
V
1.5 is expressed in cardiomyocytes [3]. A well-known blocker
of Na
V
channels is tetrodotoxin (TTX), isolated from pufferfish [4,5]. Na
V
channels are
classified as TTX-sensitive (Na
V
1.1–1.4 and 1.6–1.7), with an IC
50
in the low nM range, or
TTX-resistant (Na
V
1.5, 1.8 and 1.9), being blocked only in the μM concentration range [6].
Despite their main function in action potential generation, Na
V
channels have
been found in numerous non-excitable cell types, including astrocytes [7–10], islet β-
cells [11], keratinocytes [12], endothelial cells [13], dendritic cells [14], macrophages and
microglia [15–17], red blood cells [18], T cells [19,20] and neutrophils [21]. The functions
Cells 2022, 11, 1225. https://doi.org/10.3390/cells11071225 https://www.mdpi.com/journal/cells