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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388998%3A_____%2F24%3A00581733" target="_blank" >RIV/61388998:_____/24:00581733 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00136200

Výsledek na webu

<a href="https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP285202" target="_blank" >https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP285202</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1113/JP285202" target="_blank" >10.1113/JP285202</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physiology

ISSN

0022-3751

e-ISSN

1469-7793

Svazek periodika

602

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

18

Strana od-do

791-808

Kód UT WoS článku

001160656600001

EID výsledku v databázi Scopus

2-s2.0-85185456991