Developmental Changes in Membrane Electrical Properties of the Heart

Sperelakis, Nicholas

doi:10.1007/978-1-4613-0873-7_29

Cited by 21 publications

(11 citation statements)

References 102 publications

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“…These observations suggest that there is only a single type of Na+ channel in mouse heart cells, namely the cardiac isoform (Satin et al 1992). In contrast, Na+ currents in MCM1 cells, a cell line with cardiac-like properties derived from cells isolated from an SV40-induced tumour in the right atrium of transgenic mice, are insensitive to block by tetrodotoxin (100 /M) (Sculptoreanu, Morton, Gartside, Hauschka, Catterall & Scheuer, 1992 (Aiba & Creazzo, 1993) and in neonatal rat ventricular myocytes (Rampe & Lacerda, 1991 (Osaka & Joyner, 1992 Sperelakis (1989), then the 'Ca,L density may reflect the particular pattern of expression in a given species. The finding that ICa,L density increases during postnatal development in rabbit ventricular myocytes (Osaka & Joyner, 1991) supports this notion.…”

Section: A Comparison Of Inward Currentsmentioning

confidence: 99%

“…The variety of ICa,L densities reported in the literature may be related to differences in the pattern of L-type Ca2+ channel gene expression in different species. If the expression of L-type Ca2+ channels is developmentally regulated, as suggested by several lines of evidence summarized by Sperelakis (1989), then the 'Ca,L density may reflect the particular pattern of expression in a given species. The finding that ICa,L density increases during postnatal development in rabbit ventricular myocytes (Osaka & Joyner, 1991) supports this notion.…”

Section: A Comparison Of Inward Currentsmentioning

confidence: 99%

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Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture.

Nuss

Marbán

1994

The Journal of Physiology

132

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1. The increasing utility of transgenic mice in molecular studies of the cardiovascular system has motivated us to characterize the ionic currents in neonatal mouse ventricular myocytes. 2. Cell capacitance measurements (30 + 1 pF, n = 73) confirmed visual impressions that neonatal mouse ventricular myocytes in primary culture are considerably smaller than freshly isolated adult ventricular myocytes. With the use of electron microscopy, mitochondria and sarcoplasmic reticulum were found in close association with myofibrils, but transverse tubules were not observed. 3. Action potential durations, measured at 50 and 90% repolarization, were 23 + 1 and 42 + 2 ms respectively (n = 46). Application of 4-aminopyridine (4-AP; 5 mm) prolonged action potential duration at 50% repolarization by 26 ± 5% (n = 3). The brevity of the action potential is explained by the rapid activation of a transient outward K+ current upon voltage-clamp depolarization to plateau potentials. 4. Potassium currents identified include an inward rectifier, a large 4-AP-sensitive transient outward, a slowly inactivating 4-AP-insensitive outward, a slowly activating delayed rectifier and a small rapidly activating E-4031 (10 ,uM)-sensitive delayed rectifier K+ current. 5. Sodium currents (-305 + 50 pA pF1, n = 21) were recorded in 40 mm Na+ with Ni2+(1 mM) to block Ca2`currents and with K+ replaced by Cs+. The relative insensitivity of the Na+ current to block by tetrodotoxin (IC50 = 2'2 + 0 3 uM, n = 4) is distinctive of the cardiac Na+ channel isoform. 6 Nitrendipine-insensitive (10 /M) Ba21 currents elicited during steps from -90 to -30 mV measured -25 + 5 pA pF-1 (n = 7, 30 mm Ba2+). Decay of these currents was complete during 180 ms depolarizations, even with Ba2+ as the charge carrier. These currents were not present when the holding potential was set at -50 mV. These data support the presence of a low threshold, T-type Ca2+ current. 7. The maximal nitrendipine-sensitive L-type Ca2+ current density was -10 + 2 pA pF1 (n = 8) in 2 mm Ca2+ and -38 + 5 pA pF1 (n = 9) in 30 mm Ba2+. Exposure to isoprenaline (1/uM) resulted in an 82% increase (n=3) in the amplitude of the Ba21 currents elicited at 0 mV. 8. Neonatal mouse cardiac myocytes in primary culture possess surprisingly large inward currents given the brevity of their action potentials. Their small cell size and apparent absence of transverse tubules makes them technically favourable for whole-cell patch clamp studies. For these reasons, this preparation promises to be useful for the phenotypic characterization of transgenic mice.

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Section: A Comparison Of Inward Currentsmentioning

confidence: 99%

Section: A Comparison Of Inward Currentsmentioning

confidence: 99%

Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture.

Nuss

Marbán

1994

The Journal of Physiology

132

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“…Some quantitative differences between these and action potentials of mature rat ventricular myocytes (1, 13) can be accounted for by the immature stage of electrophysiologic development and the slowing of development by tissue culture (14)(15)(16). The postulated pacemaker function of the cluster was confirmed by the observation that pacemaker action potentials were found there exclusively.…”

Section: Discussionmentioning

confidence: 99%

Organization and Fine Structure of a Pacemaker Derived from Fetal Rat Myocardium

et al. 1995

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At an unknown point in mammalian development, cardiac precursor cells become committed to the cardiocyte phenotype. Certain of these are believed to specialize further into pacemaker cardiocytes. By culturing explanted embryonic ventricles into in vivo organ culture (Tucker DC, Snider C, Woods WT Jr: Pediatr Res 23:637-642, 1988), we observed pacemaker cells arising apparently from cardiocytes. We hypothesized that this event can be triggered by intercellular attachments, innervation, vascularization, or other factors. The present study was designed to test the hypothesis that primitive ventricular cells in the tubular heart can organize into an anatomically and electrophysiologically distinct pacemaker structure in the absence of innervation or vascularization from extrinsic sources. Developing ventricles of tubular hearts from 10-d-old rat embryos (n = 22) were excised and incubated in culture dishes. Within each explant, a group of In the developing mammalian heart, cells committed to the cardiocyte phenotype appear early, and they are initially quiescent (1, 2). At a later unknown point in development, some of these cells acquire the pacemaker phenotype. The sequence of steps between quiescent cardiocyte and spontaneously beating cardiocyte are poorly understood. This laboratory reported that 12-d-old rat ventricles explanted and cultured in oculo were quiescent in culture for 4 ? 1 d. Then spontaneous beating began, and a pacemaker locus was observed at the point of contact between cardiac tissue and the host iris (3). Growth of blood vessels, nerves, extracellular matrix, or iris tissue from the host into the explants was postulated as potential stimuli for organization of the new pacemaker. Pacemaker cells in the new center resembled those of the immature mammalian sinus node and atrioventricular node (4), suggesting that they might be precursors of the cardiac conduction system.In the present study, influences of extrinsic blood vessels, nerves, and iris tissue were eliminated by explanting embryonic rat ventricles into culture dishes instead of anterior eye Received November 30, 1993; accepted November 14, 1994

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“…5 Among other things, the primary myocardium is characterized by action potentials, which display slow depolarizations reminiscent of pacemaker action potentials and typical of slow voltage-gated calcium ion channels. 39,40 With further embryonic development, atrial and ventricular chambers that contract synchronously and sequentially begin to develop (Fig 2). 37,38 This is accompanied by the development of an adult type of ECG, which merely reflects the sequential activation of the atrial and ventricular chambers rather than the presence of a morphologically recognizable conduction system.…”

Section: Chamber Formation and The Development Of An Ecgmentioning

confidence: 99%

“…6,35,42,43 Concordantly emerging are action potentials, which have a fast rising phase and high amplitude characteristic of fast voltage-gated sodium ion channels. 39,40 Paff et al 44 concluded that in the embryonic chicken heart after 42 hours of incubation (Ϸ25 days of human development) "it would appear that a conduction system consisting of a pace-making sinuatrium, atrioventricular junctional tissue, ventricle and conus regions is developing." Thus, the authors consider the entire embryonic heart as a conducting unit without the presence of a morphologically identifiable "adult conduction system," which is in line with the view of Patten, 45 who concluded from experimental studies that "the whole of the primary myocardium constituting the wall of the myocardial tube was acting as a conducting tissue."…”

Section: Chamber Formation and The Development Of An Ecgmentioning

confidence: 99%

Development of the Cardiac Conduction System

2003

Novartis Foundation Symposia

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Developmental Changes in Membrane Electrical Properties of the Heart

Cited by 21 publications

References 102 publications

Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture.

Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture.

Organization and Fine Structure of a Pacemaker Derived from Fetal Rat Myocardium

Development of the Cardiac Conduction System

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