Analysis of subthreshold pace‐maker currents in chick embryonic heart cells.

Clay, John R.; Shrier, Alvin

doi:10.1113/jphysiol.1981.sp013639

Cited by 27 publications

(29 citation statements)

References 43 publications

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“…The If component was also included in this simulation as described in B but with as and fls as given in Clay & Shrier (1981a). That is, a = 1-05(Y+62)/(1-exp(-0-2(V+62))) and /s = 0-095 exp(0-075(V+62)).…”

Section: Discussionmentioning

confidence: 99%

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

Brochu

Clay

Shrier

1992

The Journal of Physiology

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Section: Discussionmentioning

confidence: 99%

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

Brochu

Clay

Shrier

1992

The Journal of Physiology

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“…The delayed K ϩ currents IKs and IKr have been described in reaggregates of ventricular cells (13,14,88) and atrial cells (9,88,89), in small clusters of ventricular cells (79), and in single ventricular (8) and atrial (12) cells. These currents have also been observed at the single-channel level in ventricular cells (8,67).…”

Section: Formulation Of the Modelmentioning

confidence: 99%

“…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 in reaggregates (14,16,19) or in the intact ventricle (19,97,98,118). Spontaneous beating can be abolished by addition of tetrodotoxin (TTX), a blocker of the fast inward Na ϩ current (I Na ), to the medium bathing reaggregates of trypsin-dispersed 7-day ventricular cells (16,70), but spontaneous activity continues in single cells and monolayers (57,70,81,95).…”

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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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“…The combination of a glycolysis inhibitor (iodoacetic acid) and an electron transport uncoupler (DNP) has been used, based on reports that glycolysis alone can sustain metabolism in these cells (8). The suitability of myocardial cell aggregates for microelectrode voltage clamp is well-established (9)(10)(11)(12). A principal advantage of this preparation is the relative absence of diffusion barriers, which allows the immediate effects of a test agent to be resolved (13,14).…”

mentioning

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“…The mean holding potential is -70.6 ± 8.1 mV in A, -72.0 ± 7.3 mV inB, and -67.2 ± 2.0 mV inC. current is that it results from altered behavior of the normal pacemaker mechanism. Myocardial cell aggregates have a timeand voltage-dependent pacemaker current that is similar to the 4K2 current of cardiac Purkinje fibers (11,18). In Purkinje fibers, IK2 is abolished by low concentrations of Cs' ions (19,20 Na'-free (Tris) saline (Fig.…”

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Mechanism by which metabolic inhibitors depolarize cultured cardiac cells.

Clusin¹

1983

Proc. Natl. Acad. Sci. U.S.A.

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To elucidate the means by which metabolic inhibition depolarizes cardiac cells, spontaneously beating chicken embryonic myocardial cell aggregates were voltage clamped during superfusion with 2,4-dinitrophenol and iodoacetic acid. In aggregates continuously clamped in the pacemaker potential range, abrupt exposure to these metabolic inhibitors produced a slow transient inward current. This inward current was not due to an alteration of the pacemaker current, IK2, because it could still be elicited after IK2 was abolished by Cs' ions. The inward current was increased by hyperpolarization and decreased by depolarization. It became larger and more sustained if intermittent action potentials were allowed during exposure or if the aggregates were pretreated with either 10 mM Ca2+ or 2.7 ,uM acetylstrophanthidin. The inward current was suppressed by removal of extracellular Na+ or Ca2+. These observations suggest that early depolarization of cultured cardiac cells by metabolic inhibitors involves some of the same mechanisms as the transient inward current of digitalis toxicity-specifically, an effect of intracellular Ca2+ ions on membrane permeability. Similar phenomena could occur during other forms of metabolic inhibition such as myocardial ischemia.A conspicuous effect of energy depletion in cardiac muscle is reduction of the transmembrane potential between beats. In spontaneously beating preparations, hypoxia or metabolic inhibitors produce an increase in beat frequency and reduction of the maximum diastolic potential, followed by arrest in a partially depolarized state (1). Although loss of intracellular K+ must ultimately produce depolarization in the absence of energy, it is uncertain whether this occurs rapidly enough to explain the above effects. Another early effect of metabolic inhibition in cardiac muscle is an increase in intracellular free Ca2" (1). Recordings obtained in sheep Purkinje fibers with Ca2+-sensitive microelectrodes show that 2,4-dinitrophenol (DNP) produces a marked increase in intracellular Ca2+ activity within 2 min, which parallels the decline in the membrane potential (2). Measurements of Na+-dependent 'Ca2" efflux from guinea pig myocardium indicate that cyanide has a similar effect (3). When "calcium overload" occurs in digitalis toxicity, phasic release and reuptake of sequestered intracellular Ca2+ lead to a transient inward current (TI) (4-6). This current may traverse a recently discovered cation channel, which has equal permeability to Na+ and K+ and is opened by the presence of Ca2+ at the inner surface of the cell membrane (7). Similar mechanisms might explain the early depolarizing effect of metabolic inhibition.In the present study, changes in ionic current have been recorded during application of metabolic inhibitors to chicken embryonic myocardial cell aggregates. The combination of a glycolysis inhibitor (iodoacetic acid) and an electron transport uncoupler (DNP) has been used, based on reports that glycolysis alone can sustain metabolism in these cells (8). The s...

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Analysis of subthreshold pace‐maker currents in chick embryonic heart cells.

Cited by 27 publications

References 43 publications

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

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

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

Mechanism by which metabolic inhibitors depolarize cultured cardiac cells.

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