Optogenetic confirmation of transverse-tubular membrane
excitability in intact cardiac myocytes

J 2024

Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes

SCARDIGLI, Marina, Michal PÁSEK, Lorenzo SANTINI, Chiara PALANDRI, Emilia CONTI et. al.

Basic information

Original name

Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes

Authors

SCARDIGLI, Marina, Michal PÁSEK (203 Czech Republic, belonging to the institution), Lorenzo SANTINI, Chiara PALANDRI, Emilia CONTI, Claudia CROCINI, Marina CAMPIONE, Leslie M LOEW, Antoine A F DE VRIES, Daniel A PIJNAPPELS, Francesco S PAVONE, Corrado POGGESI, Elisabetta CERBAI, Raffaele COPPINI, Peter KOHL, Cecilia FERRANTINI and Leonardo SACCONI

Edition

Journal of Physiology (London), HOBOKEN, WILEY111, 2024, 0022-3751

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1113/JP285202

UT WoS

001160656600001

Keywords in English

cardiac electrophysiology; excitation-contraction coupling; imaging

Abstract

V originále

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. imageKey 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.

Citovat

SCARDIGLI, Marina, Michal PÁSEK, Lorenzo SANTINI, Chiara PALANDRI, Emilia CONTI, Claudia CROCINI, Marina CAMPIONE, Leslie M LOEW, Antoine A F DE VRIES, Daniel A PIJNAPPELS, Francesco S PAVONE, Corrado POGGESI, Elisabetta CERBAI, Raffaele COPPINI, Peter KOHL, Cecilia FERRANTINI and Leonardo SACCONI. Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes. Journal of Physiology (London). HOBOKEN: WILEY111, 2024, vol. 602, No 5, p. 791-808. ISSN 0022-3751. Available from: https://dx.doi.org/10.1113/JP285202.

@article{2409578,
   author = {Scardigli, Marina and Pásek, Michal and Santini, Lorenzo and Palandri, Chiara and Conti, Emilia and Crocini, Claudia and Campione, Marina and Loew, Leslie M and de Vries, Antoine A F and Pijnappels, Daniel A and Pavone, Francesco S and Poggesi, Corrado and Cerbai, Elisabetta and Coppini, Raffaele and Kohl, Peter and Ferrantini, Cecilia and Sacconi, Leonardo},
   article_location = {HOBOKEN},
   article_number = {5},
   doi = {http://dx.doi.org/10.1113/JP285202},
   keywords = {cardiac electrophysiology; excitation-contraction coupling; imaging},
   language = {eng},
   issn = {0022-3751},
   journal = {Journal of Physiology (London)},
   title = {Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes},
   url = {https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP285202},
   volume = {602},
   year = {2024}
}

TY  - JOUR
ID  - 2409578
AU  - Scardigli, Marina - Pásek, Michal - Santini, Lorenzo - Palandri, Chiara - Conti, Emilia - Crocini, Claudia - Campione, Marina - Loew, Leslie M - de Vries, Antoine A F - Pijnappels, Daniel A - Pavone, Francesco S - Poggesi, Corrado - Cerbai, Elisabetta - Coppini, Raffaele - Kohl, Peter - Ferrantini, Cecilia - Sacconi, Leonardo
PY  - 2024
TI  - Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes
JF  - Journal of Physiology (London)
VL  - 602
IS  - 5
SP  - 791-808
EP  - 791-808
PB  - WILEY111
SN  - 00223751
KW  - cardiac electrophysiology
KW  - excitation-contraction coupling
KW  - imaging
UR  - https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP285202
N2  - 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. imageKey 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.
ER  -

SCARDIGLI, Marina, Michal PÁSEK, Lorenzo SANTINI, Chiara PALANDRI, Emilia CONTI, Claudia CROCINI, Marina CAMPIONE, Leslie M LOEW, Antoine A F DE VRIES, Daniel A PIJNAPPELS, Francesco S PAVONE, Corrado POGGESI, Elisabetta CERBAI, Raffaele COPPINI, Peter KOHL, Cecilia FERRANTINI and Leonardo SACCONI. Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes. \textit{Journal of Physiology (London)}. HOBOKEN: WILEY111, 2024, vol.~602, No~5, p.~791-808. ISSN~0022-3751. Available from: https://dx.doi.org/10.1113/JP285202.

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