Channel opening duration in adult muscle nAChRs determined by activated external ACh binding site

We recorded currents through the cell membrane at single nAChR molecules, held at ACh or Epibatidine (Ebd) concentrations of 0.01, 0.1, 1, 10 or 100 μM. The measured current amplitudes had an absolutely fixed value of 15 pA. This was valid for different agonists at all concentrations. Binding an agonist at one or both sites in the ring of subunits allowed to open the channel, the site that initiated the opening determined the duration of the final opening of the channel. In addition, the current flow was continuously interrupted by < 3 μs shut times. The resolution of our records was optimized to reach 5 μs, but was insufficient to resolve an unknown proportion of shorter shut times. Therefore, measured durations of openings are overestimated, and cited in brackets: τo1 (3 μs) elicited by agonist-binding at the δ-site, τo2 and τo3 (40 and 183 μs) by binding at the ϵ-site, and τo4 (752 μs) by binding at the δ- and ϵ-site. Mono-liganded nAChRs trigger short bursts of 0.6 ms duration. Bi-liganded nAChRs generate long bursts that at low agonist concentrations last 12 ms. Above 10 μM ACh, long bursts are shortened, with 100 μM ACh, to 5 ms, and further at higher concentrations. While ACh was the main agonist, Ebd bound more effectively than ACh to the ϵ-site.

Gerta Vrbová, a guide and a friend for a generation of neuro-myologists – Her scientific legacies and relations with colleagues

Gerta Sidonová - Vrbová, (Trnava, Slovakia, November 28, 1926 - London, UK, October 2, 2020) has been a key neuroscientist, who for almost half a century has contributed important findings and hypotheses on the relationships between motoneurons and skeletal muscle fibers, in particular on the differentiation and extent of plasticity of the peculiar characteristics of the different types of fibers present in mammalian muscles. This issue, Ejtm 31 (1), 2021, opens with the personal obituary authored by Dirk Pette, who remember his lifelong collaboration with Gerta, describing the many molecular and metabolic events that occur by changing the pattern of activation of adult muscle fibers through neuromuscular low frequency electrical stimulation. To honor the many scientific legacies of Gerta Vrbová and her impact on a generation of researchers studying myology and managements of neuromuscular disorders I add here additional examples of Gerta’s scientific heritage and of her relations with colleagues.

Gerta Vrbová, a guide and a friend for a generation of neuro-myologists – Her scientific legacies and relations with colleagues

Gerta Sidonová - Vrbová, (Trnava, Slovakia, November 28, 1926 - London, UK, October 2, 2020) has been a key neuroscientist, who for almost half a century has contributed important findings and hypotheses on the relationships between motoneurons and skeletal muscle fibers, in particular on the differentiation and extent of plasticity of the peculiar characteristics of the different types of fibers present in mammalian muscles. This issue, Ejtm 31 (1), 2021, opens with the personal obituary authored by Dirk Pette, who remember his lifelong collaboration with Gerta, describing the many molecular and metabolic events that occur by changing the pattern of activation of adult muscle fibers through neuromuscular low frequency electrical stimulation. To honor the many scientific legacies of Gerta Vrbová and her impact on a generation of researchers studying myology and managements of neuromuscular disorders I add here additional examples of Gerta’s scientific heritage and of her relations with colleagues.

Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells

Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cell (MuSC) activity. This ability requires the proper balance between MuSC expansion and differentiation, which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated long noncoding RNA (lncRNA), Lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, Lnc-Rewind acts as an epigenetic regulator of MuSC proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct Lnc-Rewind target. We show that Lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.