Integrative Modeling of Electrical Properties of Pacemaker Cardiac Cells

Cardiomyocytes (CMs) derived from human embryonic stem cells (hESC) provide a promising tool for the pharmaceutical industry. In this study the electrical properties and maturation of hESC-CM derived using two differentiation methods were compared and the suitability of hESC-CMs as a cell model for the assessment of drug-induced repolarization delay was evaluated. CMs were differentiated either in END-2 co-culture or by spontaneous differentiation. Action potentials (APs) were recorded from cells in spontaneously beating areas using the whole-cell patch-clamp technique. The hESC-CMs exhibited predominantly a ventricular-like phenotype with heterogeneous properties. Heterogeneity was indicative of the spectrum of hESC-CM maturation from embryonic-like with AP upstroke velocities <30 V/s and maximum diastolic potential (MDP) of close to −60 mV to more mature with values >150 V/s and −80 mV, respectively. The mean MDP was −70 mV and a significant difference was observed between the two differentiation methods (−66 versus −75 mV, P < 0.001). The age of the CMs did not correlate with phenotype maturation. The addition of the hERG blocker E-4031 and the sodium channel modulator veratridine significantly prolonged the AP duration. Furthermore, proarrhythmic indices were induced. In conclusion, the main observation was the heterogeneity in electrical properties of the hESC-CMs and this was observed with both differentiation methods. One-third of the hESC-CMs exhibited fairly mature electrophysiological properties, suggesting that mature CMs could be obtained from hESCs. However, improved differentiation methods are needed to produce homogeneous mature human CMs for pharmaceutical and toxicological applications.

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Linear electrical properties of isolated cardiac cells

The Journal of Membrane Biology ◽

10.1007/bf01868807 ◽

1984 ◽

Vol 81 (1) ◽

pp. 29-40 ◽

Cited By ~ 8

Author(s):

L. E. Moore ◽

Annerose Schmid ◽

Gerrit Isenberg

Keyword(s):

Electrical Properties ◽

Cardiac Cells ◽

Isolated Cardiac Cells

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In situ TEM measurements of the electrical properties of interface dislocations

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100131322 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1338-1339

Author(s):

F. M. Ross ◽

R. Hull ◽

D. Bahnck ◽

J. C. Bean ◽

L. J. Peticolas ◽

...

Keyword(s):

Electrical Properties ◽

Electronic Device ◽

In Situ Tem ◽

Device Performance ◽

Misfit Dislocations ◽

Electrical Characteristics ◽

Strained Layer ◽

Transmission Electron ◽

Interfacial Dislocations

We describe an investigation of the electrical properties of interfacial dislocations in strained layer heterostructures. We have been measuring both the structural and electrical characteristics of strained layer p-n junction diodes simultaneously in a transmission electron microscope, enabling us to correlate changes in the electrical characteristics of a device with the formation of dislocations.The presence of dislocations within an electronic device is known to degrade the device performance. This degradation is of increasing significance in the design and processing of novel strained layer devices which may require layer thicknesses above the critical thickness (hc), where it is energetically favourable for the layers to relax by the formation of misfit dislocations at the strained interfaces. In order to quantify how device performance is affected when relaxation occurs we have therefore been investigating the electrical properties of dislocations at the p-n junction in Si/GeSi diodes.

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The morphologies and electrical properties of indium contacts on (100) cadmium telluride surfaces

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100131747 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1422-1423

Author(s):

A.M. Letsoalo ◽

M.E. Lee ◽

E.O. de Neijs

Keyword(s):

Electrical Properties ◽

Cadmium Telluride ◽

Methanol Solution ◽

Electrical Characteristics ◽

Metal Contacts ◽

Deposition Technique ◽

Interfacial Layers ◽

Semiconductor Contacts ◽

Grown Single Crystal ◽

Diamond Abrasive

Semiconductor devices require metal contacts for efficient collection of electrical charge. The physics of these metal/semiconductor contacts assumes perfect, abrupt and continuous interfaces between the layers. However, in practice these layers are neither continuous nor abrupt due to poor nucleation conditions and the formation of interfacial layers. The effects of layer thickness, deposition rate and substrate stoichiometry have been previously reported. In this work we will compare the effects of a single deposition technique and multiple depositions on the morphology of indium layers grown on (100) CdTe substrates. The electrical characteristics and specific resistivities of the indium contacts were measured, and their relationships with indium layer morphologies were established.Semi-insulating (100) CdTe samples were cut from Bridgman grown single crystal ingots. The surface of the as-cut slices were mechanically polished using 5μm, 3μm, 1μm and 0,25μm diamond abrasive respectively. This was followed by two minutes immersion in a 5% bromine-methanol solution.

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Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166154 ◽

1996 ◽

Vol 54 ◽

pp. 738-739

Author(s):

W.G. Wier

Keyword(s):

Local Control ◽

Cardiac Tissue ◽

Cell Function ◽

Isolated Heart ◽

Cardiac Cells ◽

Confocal Imaging ◽

Ion Concentration ◽

Heart Cell ◽

Free Calcium ◽

Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

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Formation of high temperature phase in flash-evaporated SnSe films

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100176629 ◽

1990 ◽

Vol 48 (4) ◽

pp. 698-699

Author(s):

J.P.S. Hanjra

Keyword(s):

Thin Films ◽

Electrical Properties ◽

Energy Gap ◽

Dominant Role ◽

Fine Powder ◽

High Temperature Phase ◽

Temperature Phase ◽

Water Mixture ◽

Flash Evaporation ◽

Photovoltaic Applications

Tin mono selenide (SnSe) with an energy gap of about 1 eV is a potential material for photovoltaic applications. Various authors have studied the structure, electronic and photoelectronic properties of thin films of SnSe grown by various deposition techniques. However, for practical photovoltaic junctions the electrical properties of SnSe films need improvement. We have carried out investigations into the properties of flash evaporated SnSe films. In this paper we report our results on the structure, which plays a dominant role on the electrical properties of thin films by TEM, SEM, and electron diffraction (ED).Thin films of SnSe were deposited by flash evaporation of SnSe fine powder prepared from high purity Sn and Se, onto glass, mica and KCl substrates in a vacuum of 2Ø micro Torr. A 15% HF + 2Ø% HNO3 solution was used to detach SnSe film from the glass and mica substrates whereas the film deposited on KCl substrate was floated over an ethanol water mixture by dissolution of KCl. The floating films were picked up on the grids for their EM analysis.

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