Analysis of the T-type calcium channel in embryonic chick ventricular myocytes

Kawano, Seiko; DeHaan, Robert L.

doi:10.1007/bf01871667

Cited by 18 publications

(11 citation statements)

References 40 publications

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“…In adult preparations, the unitary conductance ofI r is only about one-third that OflL [5,13], and the whole-cell Ir current magnitude is only onehalf to one-tenth that of IL [16,19,20]. We have recently shown that 14-day embryonic chick ventricle cells have both IL and Iv, with electrical and pharmacological properties that resemble those in adult mammalian cardiac preparations at both the whole-cell and single-channel levels [22,23]. In these differentiating cells, the unitary conductance of the I r channel is also substantially smaller than that ofl L [23], but the I r whole-cell current is roughly twice as large as IL [22], apparently because I c normally opens in a flickering mode with a low openstate probability [27a].…”

Section: Introductionmentioning

confidence: 94%

“…In the mammalian heart, I L is the major component of the slow inward current that maintains the plateau phase of the cardiac action potential [7,28], and its electrical and permeation properties have been studied extensively [32,37]. The I L channel has a unitary conductance near 20 pS with 90-110 mMBa 2+ as the charge carrier [13,16] or 50-100 pS when passing Na--in the absence of divalent cations [23,26,27,36]. The channel is modulated by/3-adrenoceptor agonists [4,21], it is blocked by phenylalkylamines such as verapamil or D600 [7], and it is sensitive to dihydropyridine antagonists such as nifedipine [4,16] and agonists such as Bay K-8644 [4,25].…”

Section: Introductionmentioning

confidence: 99%

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Developmental changes in the calcium currents in embryonic chick ventricular myocytes

Kawano

DeHaan

1991

J. Membrain Biol.

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Using the patch-clamp technique, we recorded whole-cell calcium current from isolated cardiac myocytes dissociated from the apical ventricles of 7-day and 14-day chick embryos. In 70% of 14-day cells after 24 hr in culture, two component currents could be separated from total ICa activated from a holding potential (Vh) of -80 mV. L-type current (IL) was activated by depolarizing steps from Vh -30 or -40 mV. The difference current (IT) was obtained by subtracting IL from ICa. IT could also be distinguished pharmacologically from IL in these cells. IT was selectively blocked by 40-160 microM Ni2+, whereas IL was suppressed by 1 microM D600 or 2 microM nifedipine. The Ni2(+)-resistant and D600-resistant currents had activation thresholds and peak voltages that were near those of IT and IL defined by voltage threshold, and resembled those in adult mammalian heart. In 7-day cells, IT and IL could be distinguished by voltage threshold in 45% (S cells), while an additional 45% of 7-day cells were nonseparable (NS) by activation voltage threshold. Nonetheless, in most NS cells, ICa was partly blocked by Ni2+ and by D600 given separately, and the effects were additive when these agents were given together. Differences among the cells in the ability to separate IT and IL by voltage threshold resulted largely from differences in the position of the steady-state inactivation and activation curves along the voltage axis. In all cells at both ages in which the steady-state inactivation relation was determined with a double-pulse protocol, the half-inactivation potential (V1/2) of the Ni2(+)-resistant current IL averaged -18 mV. In contrast, V1/2 of the Ni2(+)-sensitive IT was -60 mV in 14-day cells, -52 mV in 7-day S cells, and -43 mV in 7-day NS cells. The half-activation potential was near -2 mV for IL at both ages, but that of IT was -38 mV in 14-day and -29 mV in 7-day cells. Maximal current density was highly variable from cell to cell, but showed no systematic differences between 7-day and 14-day cells. These results indicate that the main developmental change that occurs in the components of ICa is a negative shift with embryonic age in the activation and inactivation relationships of IT along the voltage axis.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Developmental changes in the calcium currents in embryonic chick ventricular myocytes

Kawano

DeHaan

1991

J. Membrain Biol.

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“…ICa has been described in 7-day reaggregates of ventricular cells (72), in small clusters of ventricular cells (28,79), in single ventricular cells (13,28,42,44), and at the single-channel level (43,68). In one laboratory, L-type ICa (ICa,L) was found in 11 of 12 6-day ventricular cells, and T-type ICa (ICa,T) was found in the remaining cell (13).…”

Section: Formulation Of the Modelmentioning

confidence: 99%

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

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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...

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“…LVA Ca 2ϩ currents are expressed in embryonic heart and postnatal atrial myocytes, but in many species they are small or absent in adult ventricular myocytes (15,44) and are expressed differentially across the myocardial wall (42). Reexpression of LVA current and an increase in LVA Ca 2ϩ current density are common findings in hypertrophied or enlarged cardiac muscle.…”

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confidence: 99%

Disruption of growth hormone secretion alters Ca²⁺current density and expression of Ca²⁺channel and insulin-like growth factor genes in rat atria

Larsen¹,

Chen²,

Best³

2005

American Journal of Physiology-Heart and Circulatory Physiology

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The influence of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis on expression of low-voltage-activated (LVA) Ca2+ current in atrial tissue was investigated using spontaneous dwarf (SpDwf) rats, a mutant strain that lacks GH. Atrial myocytes from SpDwf rats express LVA and high-voltage-activated (HVA) Ca2+ currents and the Ca2+ channel α1-subunit genes CaV1.2, CaV2.3, CaV3.1, and CaV3.2. LVA current density decreases significantly beginning at, or shortly after, birth in normal animals; however, its density is maintained in SpDwf rats at 1 pA/pF for ≥12 wk after birth. The abundance of mRNAs encoding CaV2.3 and CaV3.2 declines with advancing age in normal atrial development, yet expression of CaV2.3 mRNA remains significantly elevated in older SpDwf animals. Quantitation of local transcript levels for mRNAs encoding IGF-I and IGF-I receptor (IGF-IR) also reveals significant differences in expression of these transcripts in atrial tissue of SpDwf animals compared with controls. In SpDwf rats, the abundance of IGF-IR mRNA remains elevated at many postnatal ages, whereas mRNA encoding IGF-I is maintained only in older animals. Physiological concentrations of IGF-I cause two- to threefold increases in LVA current density in primary cultures of atrial myocytes, and this effect is blocked by an antisense oligonucleotide targeting the IGF-IR. Thus disruption of GH production in SpDwf animals alters expression of atrial LVA Ca2+ channel and IGF genes as well as postnatal regulation of LVA Ca2+ current density, most likely acting through compensatory mechanisms via the local IGF-IR.

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Analysis of the T-type calcium channel in embryonic chick ventricular myocytes

Cited by 18 publications

References 40 publications

Developmental changes in the calcium currents in embryonic chick ventricular myocytes

Developmental changes in the calcium currents in embryonic chick ventricular myocytes

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

Disruption of growth hormone secretion alters Ca²⁺current density and expression of Ca²⁺channel and insulin-like growth factor genes in rat atria

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Analysis of the T-type calcium channel in embryonic chick ventricular myocytes

Cited by 18 publications

References 40 publications

Developmental changes in the calcium currents in embryonic chick ventricular myocytes

Developmental changes in the calcium currents in embryonic chick ventricular myocytes

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

Disruption of growth hormone secretion alters Ca2+current density and expression of Ca2+channel and insulin-like growth factor genes in rat atria

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Disruption of growth hormone secretion alters Ca²⁺current density and expression of Ca²⁺channel and insulin-like growth factor genes in rat atria