It has been suggested in a previous article [Escande et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H843-H850, 1985] that transient outward currents may participate in the initial repolarization of human atrial fibers. The present study substantiates the existence of such currents in human myocardium. Membrane currents were recorded in enzymatically dissociated cells using the whole cell patch-clamp technique. Two kinds of transient outward currents were observed: 1) a long-lasting outward current, (ilo), which was suppressed by 4-aminopyridine. The time to peak of ilo was 18.0 +/- 0.7 ms, and its inactivation time constant was 35.7 +/- 2.1 ms at room temperature (test pulses, +20 mV; holding potential, -40 mV); 2) a brief outward current (ibo), which persisted with 3 mM 4-aminopyridine and exhibited a shorter time to peak (5.5 +/- 0.2 ms) and a faster decay (time constant, 9.1 +/- 1.8 ms). ilo was inhibited by Ba but was insensitive to the calcium blocker Co. Co blocked both the slow inward current (isi) and ibo. It is concluded that two different transient outward currents control the repolarization in human atrial cells.

Key point• Fibroblasts play a major role in heart physiology. In pathological conditions, they can lead to cardiac fibrosis when they differentiate into myofibroblasts.• This differentiated status is associated with changes in expression profile leading to neo-expression of proteins such as ionic channels.• The present study investigates electrophysiological changes associated with fibroblast differentiation focusing on voltage-gated sodium channels in human atrial fibroblasts and myofibroblasts.• We show that human atrial fibroblast differentiation in myofibroblasts is associated with de novo expression of voltage gated sodium current. Multiple arguments support that this current is predominantly supported by the Na v 1.5 α-subunit which may generate a persistent sodium entry into myofibroblasts.• Our data revealed that Na v 1.5 α-subunit expression is not restricted to cardiac myocytes within the atrium. Since fibrosis is one of the fundamental mechanisms implicated in atrial fibrillation, it is of great interest to investigate how this channel could influence myofibroblasts function.Abstract 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.

The aim of this work is to evaluate the impact on the rat microbiota of long-term feeding with phenolic compounds (PC) rich grape pomace extracts. Thirty, 2-mo-old rats, were divided into 5 groups. Four groups were treated with different concentrations of PC (2.5, 5, 10, and 20 mg/kg/d diluted in 0.1% DMSO), and 1 group received 0.1% Dimethyl Sulfoxide (DMSO) alone (control group). The daily treatment lasted 14 mo. Major phenolic compounds constituents were characterized by the high-performance liquid chromatography and free radical scavenging capacity was measured by means of the DPPH assay. Fecal samples from young rats (2-mo old), and rats daily fed with PC or DMSO were collected at 6 and 14 mo posttreatment. The gut microbiota composition was analyzed by quantitative polymerase chain reaction. Bifidobacterium was significantly higher in the groups PC 2.5 and PC 5 than in control and young rats. Lactobacillus decreased with time in all treated and untreated groups. Bacteroides, Clostridium leptum subgroup (Clostridium cluster IV), and Enterococcus were not significantly changed by PC at any concentration when compared to control; nevertheless, after 14 mo of treatment all concentrations of PC abolished the increase of Clostridium sensu stricto (cluster I) (Clostridium Cluster I) observed in the control group when compared to young rats. PC do modulate selectively rat gut microbiome to a healthier phenotype in long-term feeding rats, and could counteract the adverse outcomes of aging on gut bacterial population.Keywords: aging, gut microbiota, phenolic compoundsPractical Application: This research shows that phenolic-rich grape pomace extracts exhibiting a high antioxidant activity, selectively modulate rat gut microbiota to a healthier phenotype within age in a long-term feeding rats.