A distinct de novo expression of Nav1.5 sodium channels in human atrial fibroblasts differentiated into myofibroblasts.
Fibroblasts play a major role in heart physiology. They are at the origin of the extracellular matrix renewal and production of various paracrine and autocrine factors. In pathological conditions, fibroblasts proliferate, migrate and differentiate into myofibroblasts leading to cardiac fibrosis. This differentiated status is associated with changes in expression profile leading to neo-expression of proteins such as ionic channels. The present study investigates further electrophysiological changes associated with fibroblast differentiation focusing on the activity of voltage-gated sodium channels in human atrial fibroblasts and myofibroblasts. Using the patch clamp technique we show that human atrial myofibroblasts display a fast inward voltage gated sodium current with a density of 13.28 ± 2.88 pA pF(-1) whereas no current was detectable in non-differentiated fibroblasts. Quantitative RT-PCR reveals a large amount of transcripts encoding the Na(v)1.5 α-subunit with a fourfold increased expression level in myofibroblasts when compared to fibroblasts. Accordingly, half of the current was blocked by 1 μm of tetrodotoxin and immunocytochemistry experiments reveal the presence of Na(v)1.5 proteins. Overall, this current exhibits similar biophysical characteristics to sodium currents found in cardiac myocytes except for the window current that is enlarged for potentials between -100 and -20 mV. Since fibrosis is one of the fundamental mechanisms implicated in atrial fibrillation, it is of great interest to investigate how this current could influence myofibroblast properties. Moreover, since several Na(v)1.5 mutations are related to cardiac pathologies, this study offers a new avenue on the fibroblasts involvement of these mutations.
Institut de Physiologie et Biologie Cellulaires, FRE 3511, CNRS/Université de Poitiers, Poitiers, France. aurelien.chatelier@univ-poitiers.fr
Aurélien
A
Chatelier
Aurélie
A
Mercier
Boris
B
Tremblier
Olivier
O
Thériault
Majed
M
Moubarak
Najate
N
Benamer
Pierre
P
Corbi
Patrick
P
Bois
Mohamed
M
Chahine
Jean François
JF
Faivre
D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006325:Heart Atria / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D062554:NAV1.5 Voltage-Gated Sodium Channel; D021122:Protein Subunits; C568320:SCN5A protein, human