Developmental change in fast Na channel properties in embryonic chick ventricular heart cells

Sada, Hideaki; Ban, Takashi; Fujita, Takeshi; Ebina, Yoshio; Sperelakis, Nicholas

doi:10.1139/y95-205

Cited by 17 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is voltage-clamp evidence for the existence of INa in reaggregates of 7-to 11-day ventricular cells (22,72), in single 2-to 18-day ventricular cells (29,40,82,83,112), and at the single-channel level in 7-day ventricular cells (64,112). Voltage-clamp studies of 7-day ventricular clusters in our laboratory show a fast inward current upon a depolarizing clamp step from potentials more hyperpolarized than about Ϫ60 mV.…”

Section: Currents Not Included In the Ionic Modelmentioning

confidence: 62%

“…Very early during development (3 days), the steady-state inactivation curve of I Na is shifted in the depolarizing direction (82); simulations suggest that the window component of I Na might then contribute to diastolic depolarization (83). I st has been reported during diastolic depolarization in spontaneously active single SA node cells (71, but see Ref.…”

Section: Currents Underlying Diastolic Depolarization In the Modelmentioning

confidence: 99%

“…9, A and B). The MDP (Ϫ60 mV in the clusters and Ϫ67 mV in the model) is sufficiently depolarized to essentially render I Na fully inactivated, because the foot of the INa steady-state inactivation curve lies at about Ϫ50 to Ϫ60 mV in 7-day ventricular reaggregates (22) and 7-day ventricular cells (29,82). Indeed, addition of I Na to our model, on the basis of the conductance and the activation and inactivation curves from single 7-day ventricular cells (29) and the time constants from 11-day reaggregates (22), slightly increases V max from 9.5 to 10.2 V/s.…”

Section: Currents Not Included In the Ionic Modelmentioning

confidence: 99%

See 2 more Smart Citations

An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells

Krogh‐Madsen

Schäffer²,

Skriver³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

We recorded transmembrane potential in whole cell recording mode from small clusters (2-4 cells) of spontaneously beating 7-day embryonic chick ventricular cells after 1-3 days in culture and investigated effects of the blockers D-600, diltiazem, almokalant, and Ba 2ϩ . Electrical activity in small clusters is very different from that in reaggregates of several hundred embryonic chick ventricular cells, e.g., TTX-sensitive fast upstrokes in reaggregates vs. TTX-insensitive slow upstrokes in small clusters (maximum upstroke velocity ϳ100 V/s vs. ϳ10 V/s). On the basis of our voltageand current-clamp results and data from the literature, we formulated a Hodgkin-Huxley-type ionic model for the electrical activity in these small clusters. The model contains a Ca 2ϩ current (ICa), three K ϩ currents (IKs, IKr, and IK1), a background current, and a seal-leak current. ICa generates the slow upstroke, whereas IKs, IKr, and IK1 contribute to repolarization. All the currents contribute to spontaneous diastolic depolarization, e.g., removal of the seal-leak current increases the interbeat interval from 392 to 535 ms. The model replicates the spontaneous activity in the clusters as well as the experimental results of application of blockers. Bifurcation analysis and simulations with the model predict that annihilation and single-pulse triggering should occur with partial block of I Ca. Embryonic chick ventricular cells have been used as an experimental model to investigate various aspects of spontaneous beating of cardiac cells, e.g., mutual synchronization, regularity of beating, and spontaneous initiation and termination of reentrant rhythms; our model allows investigation of these topics through numerical simulation.pacemaker; seal-leak current; rapid delayed rectifier potassium current block; slow inward calcium current block; bifurcation analysis SPONTANEOUS ACTIVITY based on generation of the pacemaker potential (spontaneous phase 4, or diastolic, depolarization) is not normally found in adult ventricular muscle in situ, nor is it normally found in single cells freshly isolated from adult ventricular muscle. In contrast, early enough during development, ventricular muscle (or areas of the heart destined to eventually become ventricular muscle) can beat spontaneously (1, 97). Spontaneous electrical activity can also be seen in single cells and in small clusters of cells isolated from the embryonic chick ventricle (10,17,26,49,51,78,95), in the embryonic mouse ventricle (117), and in the neonatal rat ventricle (86).After a couple of days in culture, the electrical activity in an isolated embryonic chick ventricular cell, in a small cluster of a few such cells, or in a sparse monolayer is very different from that in situ or in a reaggregate of hundreds or thousands of cells isolated from the ventricle. For example, when trypsin-dispersed ventricular cells from 7-day embryonic chick hearts are used, the upstroke velocity is much lower in single cells, in small clusters of cells, and in sparse monolayers (17,49,51,95) than...

show abstract

Section: Currents Not Included In the Ionic Modelmentioning

confidence: 62%

Section: Currents Underlying Diastolic Depolarization In the Modelmentioning

confidence: 99%

Section: Currents Not Included In the Ionic Modelmentioning

confidence: 99%

See 1 more Smart Citation

An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells

Krogh‐Madsen

Schäffer²,

Skriver³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…2C), I Na in hiPSC-CM showed similar fractions of maximal availability and conductance (1.4% and 1.8% for EHT and ML, respectively) as human adult CM (~2% and ~1% for atrial 17 and ventricular CM 16 , respectively). It should be noted that the amount of window current might be an additional marker in the maturation process, since window currents decrease during the development of chick embryonic CM 32 .…”

Section: Discussionmentioning

confidence: 99%

Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density

Lemoine

Mannhardt

Breckwoldt

et al. 2017

Sci Rep

152

124

View full text Add to dashboard Cite

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with greater resemblance to human heart tissue in comparison to standard technique of 2D monolayer (ML) format. INa was measured in ML or EHT using the standard patch-clamp technique. INa density was ~1.8 fold larger in EHT (−18.5 ± 1.9 pA/pF; n = 17) than in ML (−10.3 ± 1.2 pA/pF; n = 23; p < 0.001), approaching densities reported for human CM. Inactivation kinetics, voltage dependency of steady-state inactivation and activation of INa did not differ between EHT and ML and were similar to previously reported values for human CM. Action potential recordings with sharp microelectrodes showed similar upstroke velocities in EHT (219 ± 15 V/s, n = 13) and human left ventricle tissue (LV, 253 ± 7 V/s, n = 25). EHT showed a greater resemblance to LV in CM morphology and subcellular NaV1.5 distribution. INa in hiPSC-CM showed similar biophysical properties as in human CM. The EHT format promotes INa density and action potential upstroke velocity of hiPSC-CM towards adult values, indicating its usefulness as a model for excitability of human cardiac tissue.

show abstract

“…Hippocampal astrocytes show a pronounced negative shift in the h inf curve for the Na ϩ current during development, probably due to a developmental switch in Na ϩ channel types (551). Chick cardiac ventricular muscle cells also show a negative shift in the h inf curve of the Na ϩ current with development, which reduces the overlap, or window current, where the activation and inactivation curves overlap (514). The large window current early in development triggers spontaneous activity, which is absent in the mature cells.…”

Section: A Immature Voltage-gated Channels With Properties Differentmentioning

confidence: 99%

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

Moody¹,

Bosma²

2005

Physiological Reviews

344

323

View full text Add to dashboard Cite

At specific stages of development, nerve and muscle cells generate spontaneous electrical activity that is required for normal maturation of intrinsic excitability and synaptic connectivity. The patterns of this spontaneous activity are not simply immature versions of the mature activity, but rather are highly specialized to initiate and control many aspects of neuronal development. The configuration of voltage- and ligand-gated ion channels that are expressed early in development regulate the timing and waveform of this activity. They also regulate Ca2+ influx during spontaneous activity, which is the first step in triggering activity-dependent developmental programs. For these reasons, the properties of voltage- and ligand-gated ion channels expressed by developing neurons and muscle cells often differ markedly from those of adult cells. When viewed from this perspective, the reasons for complex patterns of ion channel emergence and regression during development become much clearer.

show abstract

Developmental change in fast Na channel properties in embryonic chick ventricular heart cells

Cited by 17 publications

References 13 publications

An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells

An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells

Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

Contact Info

Product

Resources

About