Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart.

Brochu, Richard M.; Clay, John R.; Shrier, Alvin

doi:10.1113/jphysiol.1992.sp019276

Cited by 28 publications

(15 citation statements)

References 24 publications

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“…The current was observed in cultures from seven day embryonic ventricles, but markedly reduced in those obtained from 17 day embryos. A 1992 report from these authors [1] confirmed that the current was indeed i f . The conclusion was that i f was indeed present in young embryonic ventricle, but expression was lost during development.…”

Section: Introductionmentioning

confidence: 86%

“…Until recently, however, there was agreement that i f was present in all regions of the heart that show spontaneous activity, including the sinus node, latent atrial pacemakers, and Purkinje fibers, but absent from ventricular tissue. Recent reports have questioned this fundamental premise concerning the absence of i f in the normally quiescent ventricle [1,7]. The first evidence for i f in the ventricle actually dates to 1980, when Shrier and Clay [5] reported a current with strikingly similar voltage and time dependence to i f in embryonic chick ventricle.…”

Section: Introductionmentioning

confidence: 99%

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Developmental change in the voltage-dependence of the pacemaker current, i f , in rat ventricle cells

Robinson

Chang

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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Myocytes were isolated from newborn and adult rat ventricle. Using the whole-cell patch clamp, the two cell populations were compared for the presence of the hyperpolarization-activated pacemaker current if. As in other mammalian species, the threshold voltage in acutely dissociated adult rat myocytes was extremely negative (-113 +/- 5 mV; n=12). In contrast, threshold in newborn cells was relatively positive, regardless of whether measured in acutely dissociated (-72 +/- 2 mV; n=6) or cultured cells (-70 +/- 2 mV; n=9). Current density was not reduced in the adult. These results suggest that with development the ventricle assumes its non-pacemaker function, at least in part, by a shift of the voltage dependence of if outside the physiological range.

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Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Developmental change in the voltage-dependence of the pacemaker current, i f , in rat ventricle cells

Robinson

Chang

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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“…On the basis of the conductance, reversal potential, kinetics, and activation curve described in Ref. 5, we find that addition of I f to the model causes only a very slight decrease in IBI from 392 to 390 ms. The MDP in our cells is, hence, too depolarized for I f to activate and contribute significantly to pacemaking activity; therefore, we do not include it in our model.…”

Section: Currents Not Included In the Ionic Modelmentioning

confidence: 95%

“…The pacemaker current (I f) has been reported in ventricular reaggregates (4,14,15,87,88) as well as in single atrial and ventricular cells and small clusters of such cells (4,5,85). The midpoint of the activation range of I f is ϳ30 mV more negative in single ventricular cells and small clusters than in reaggregates, with the foot of the activation curve of this hyperpolarization-activated current lying at Ϫ70 mV in single cells and small clusters (5). In our clusters, we find I f activated at potentials negative to Ϫ70 mV (79).…”

Section: Currents Not Included In the Ionic 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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“…Of course, this does not necessarily exclude the possibility that other currents such as if current also may contribute to the pacemaker depolarizations in the ventricular cells of young embryos. However, the if current in this tissue likely flows in a more negative potential range (Vm <-60 mV) (7,13).…”

Section: Discussionmentioning

confidence: 99%

Role of the Steady-State Na+ Channel Current in Pacemaker Depolarizations in Young Embryonic Chick Ventricular Myocytes

Sada¹,

Ban²,

Fujita

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-To assess the age-related changes in kinetic properties of the cardiac Na+ channel, whole-cell voltage-clamp (v-c) experiments were conducted using 3-, 10-and 17-day-old embryonic chick ventricular heart cells. In line with the first-order kinetic model, kinetic parameters for the activation and inactivation of the channel were determined from the v-c results. Simulation studies using kinetic parameters so determined have reproduced the current-voltage relations and the steady-state inactivation characteristics observed in cells in the three age groups. The rate of depolarization of the simulated action potentials was also comparable to that experimentally recorded. In conclusion, the steady-state Na+ conductance can play a significant role in the automatic depolarizations observed in young embryonic ventricular cells.Keywords: Heart, Voltage-clamp, Development, Automaticity, Simulation Depression of cardiac pacemaker activity is a common property shared among all class-1 antiarrhythmic agents (1), but it has been questioned if the major action of these drugs, their Na+ channel blocking action, is responsible for the depression, since the Na+ channels contribute little to the pacemaker depolarizations due to the low channel density as well as their inactivation in the range of pacemaker potentials.The fast Na+ channel properties change during development. Above all, the presence of the automatic activities and slow rate of rise of action potential (AP) in ventricular cells is characteristic only in an early stage of development (see ref. 2 for a review). In the previous voltageclamp (v-c) study using cultured heart cells from 3-, 10-and 17-day-old embyronic chick ventricles (3), we quantified the developmental changes in the activation and inactivation kinetics parameters. In the study, we found that the steady-state (window) conductance of the Na+ channel at ca. -40 mV in the young (3-day) heart was 0.6010 of the maximum conductance (gNa), and suggested that the current in this magnitude was large enough to induce the pacemaker depolarization. To provide evidence for the involvement of the window conductance in automatic depolarizations in this tissue, further v-c experiments were carried out for the three age groups, with special reference to the inactivation kinetics over a whole potential range, to enable the simulation study. We report here that the Na+ window current plays an important role in the slow depolarization during the diastole in ventricular cells of young embryos. MATERIALS AND METHODS Experimental proceduresThe hearts from 3-, 10-and 17-day-old chick embryos were dissected under sterile conditions. The procedures for cell separation and cultivation were similar to the previously reported ones (3 -5). The use of fertilized eggs for the v-c experiments was approved and authorized by the Animal Experiment Committee, Yamaguchi University, School of Medicine. Glass pipette electrodes were fabricated by a two-step pulling of Pyrex glass capillary tubes (o.d. =1.4 mm), and each electrode was ...

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Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart.

Cited by 28 publications

References 24 publications

Developmental change in the voltage-dependence of the pacemaker current, i f , in rat ventricle cells

Developmental change in the voltage-dependence of the pacemaker current, i f , in rat ventricle cells

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

Role of the Steady-State Na+ Channel Current in Pacemaker Depolarizations in Young Embryonic Chick Ventricular Myocytes

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