E-viri
Recenzirano
Odprti dostop
-
Scardigli, Marina; Pásek, Michal; Santini, Lorenzo; Palandri, Chiara; Conti, Emilia; Crocini, Claudia; Campione, Marina; Loew, Leslie M.; Vries, Antoine A. F.; Pijnappels, Daniël A.; Pavone, Francesco S.; Poggesi, Corrado; Cerbai, Elisabetta; Coppini, Raffaele; Kohl, Peter; Ferrantini, Cecilia; Sacconi, Leonardo
Journal of physiology, 1 March 2024, 2024-Mar, 2024-03-00, 20240301, Letnik: 602, Številka: 5Journal Article
T‐tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well‐co‐ordinated excitation–contraction coupling (ECC) and thus homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarization is active (local generation of action potentials; AP) or passive (following depolarization of the outer cell surface sarcolemma; SS) has not been experimentally validated in cardiomyocytes. Based on the assessment of ion flux pathways needed for AP generation, we hypothesize that TT are excitable. We therefore explored TT excitability experimentally, using an all‐optical approach to stimulate and record trans‐membrane potential changes in TT that were structurally disconnected, and hence electrically insulated, from the SS membrane by transient osmotic shock. Our results establish that cardiomyocyte TT can generate AP. These AP show electrical features that differ substantially from those observed in SS, consistent with differences in the density of ion channels and transporters in the two different membrane domains. We propose that TT‐generated AP represent a safety mechanism for TT AP propagation and ECC, which may be particularly relevant in pathophysiological settings where morpho‐functional changes reduce the electrical connectivity between SS and TT membranes. Key points Cardiomyocytes are characterized by a complex network of membrane invaginations (the T‐tubular system) that propagate action potentials to the core of the cell, causing uniform excitation–contraction coupling across the cell. In the present study, we investigated whether the T‐tubular system is able to generate action potentials autonomously, rather than following depolarization of the outer cell surface sarcolemma. For this purpose, we developed a fully optical platform to probe and manipulate the electrical dynamics of subcellular membrane domains. Our findings demonstrate that T‐tubules are intrinsically excitable, revealing distinct characteristics of self‐generated T‐tubular action potentials. This active electrical capability would protect cells from voltage drops potentially occurring within the T‐tubular network. figure legend Methodological framework employed to dissect the electrical properties of isolated t‐tubules (TT). Isolated cardiomyocytes with specific expression of ChR2 (ChR2 CM) are initially stained with a voltage‐sensitive dye (VSD) suitable for two‐photon imaging, thus allowing TT labelling and imaging. Subsequently, TTs are disconnected from the superficial sarcolemma using a formamide‐based osmotic shock, and the electrical activity of isolated TTs is probed using a random‐access two‐photon microscope during optogenetic stimulation. This approach allowed the first recording of self‐generated T‐tubular action potentials (TT AP) in cardiac cells.
Avtor
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.