A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse–axial tubular system

Pásek, Michal; Šimurda, Jiří; Orchard, Clive H.; Christé, Georges

doi:10.1016/j.pbiomolbio.2007.07.022

Cited by 56 publications

(65 citation statements)

References 45 publications

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“…The uniformity of AP in all sarcolemma domains is maintained even at high pacing rates (Fig. S3), confirming the expected tight electrical coupling between membrane domains (16,17). The tight electrical coupling also holds in the subthreshold voltage range during spontaneous depolarization events (Fig.…”

Section: Resultssupporting

confidence: 70%

“…This indicates that the structural integrity of the TATS is crucial to maintaining a functional electrical coupling between the TATS and SS. In agreement with a validated mathematical model (16), the electrical coupling between SS and TATS can be quantified in terms of a mean resistance (R) of the tubular system. Taking into account that the TATS represents a parallel combination of TTs, R ∝ 1 = n TT , where n TT is the number of attached TTs.…”

Section: Discussionmentioning

confidence: 85%

“…This can increase the probability that the depolarization wavefront propagating from the surface to TATS fails in reaching the AP threshold in the tubular membrane. To confirm this scenario, we used a computational model of rat ventricular myocyte (16) to predict how TATS structural alterations affect AP propagation. We find that when n TT is markedly reduced, even small variations in tubular geometry (e.g., tubular stenosis and/or an increment of the effective tubular length related to the reduction in t-tubular mouths) can cause AP propagation failure (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Action potential propagation in transverse-axial tubular system is impaired in heart failure

Sacconi

Ferrantini

Lotti

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

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The plasma membrane of cardiac myocytes presents complex invaginations known as the transverse-axial tubular system (TATS). Despite TATS's crucial role in excitation-contraction coupling and morphological alterations found in pathological settings, TATS's electrical activity has never been directly investigated in remodeled tubular networks. Here we develop an ultrafast random access multiphoton microscope that, in combination with a customly synthesized voltage-sensitive dye, is used to simultaneously measure action potentials (APs) at multiple sites within the sarcolemma with submillisecond temporal and submicrometer spatial resolution in real time. We find that the tight electrical coupling between different sarcolemmal domains is guaranteed only within an intact tubular system. In fact, acute detachment by osmotic shock of most tubules from the surface sarcolemma prevents AP propagation not only in the disconnected tubules, but also in some of the tubules that remain connected with the surface. This indicates that a structural disorganization of the tubular system worsens the electrical coupling between the TATS and the surface. The pathological implications of this finding are investigated in failing hearts. We find that AP propagation into the pathologically remodeled TATS frequently fails and may be followed by local spontaneous electrical activity. Our findings provide insight on the relationship between abnormal TATS and asynchronous calcium release, a major determinant of cardiac contractile dysfunction and arrhythmias.cardiac disease | nonlinear microscopy | voltage imaging | t tubules T he transverse-axial tubular system (TATS) is a complex network characterized by transverse (t tubules, TT) and longitudinal (axial tubules, AT) components running from one transverse tubule to the next (1-3). The TATS of a myocyte rapidly conducts depolarization of the surface sarcolemma (SS) to the core of the cardiomyocyte (4). The coupling between sarcolemmal Ca 2+ entry during an action potential (AP) and Ca 2+ release from sarcoplasmic reticulum (SR) promotes synchronous myofibril activation throughout the myocyte (5). Recent studies highlight that AP-relevant ion channels and transporters are expressed in TATS membrane with different densities and isoforms from those in SS (6, 7). These findings, in combination with diffusional limitations in TATS's lumen (3,8), raise the possibility that AP may differ among membrane domains. Further interest in the TATS AP stems from the recent finding of loss and disorganization of tubules in several pathological conditions, including heart failure (9-14). Because correlation between morphological TATS alterations and Ca 2+ -release asynchronicity has been observed (14, 15), recording AP propagation in TATS can elucidate the fundamental electrophysiological mechanism linking structural and functional anomalies.Although the uniformity of the AP across the whole sarcolemma has been mathematically (16) and experimentally (17) proved, a potential alteration of the AP propagation i...

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Section: Resultssupporting

confidence: 70%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Action potential propagation in transverse-axial tubular system is impaired in heart failure

Sacconi

Ferrantini

Lotti

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

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“…This intention is supported by recent developments in the mathematical description of mitochondrial calcium dynamics (Nguyen et al 2007). Most recently Pásek et al (Pásek et al 2008a, Pásek et al 2008b have developed compartmental models that explicitly include the transverse-axial tubular system. These models have been applied to assess the importance of ion channel heterogeneity and restricted diffusion within the tubular system on physiological function.…”

Section: Models Of Calcium Signalling In Cardiac Cellsmentioning

confidence: 99%

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

Fink

Niederer

Cherry

et al. 2011

Progress in Biophysics and Molecular Biology

149

136

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In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field.

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“…(Marder & Taylor, 2011) It has been known that discrepancies exist between the model simulations and the AP-clamp measured current (Banyasz et al, 2011), and model simulations still fail to reproduce some important AP dynamic behaviors (i.e. EAD, adaptation, restitution) Faber et al, 2007;Mahajanaw et al, 2008;Pasek et al, 2008).…”

Section: Study Of the Individual Cell Electrophysiology (Ice)mentioning

confidence: 99%

From Action Potential-Clamp to "Onion-Peeling" Technique – Recording of Ionic Currents Under Physiological Conditions

Chen‐Izu¹,

Izu²,

Nánási³

et al. 2012

Patch Clamp Technique

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A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse–axial tubular system

Cited by 56 publications

References 45 publications

Action potential propagation in transverse-axial tubular system is impaired in heart failure

Action potential propagation in transverse-axial tubular system is impaired in heart failure

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

From Action Potential-Clamp to "Onion-Peeling" Technique – Recording of Ionic Currents Under Physiological Conditions

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