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A Shrier

Publications and source records attributed to A Shrier.

61 records · Page 4Linked to original sources

Phase locking, period-doubling bifurcations, and irregular dynamics in periodically stimulated cardiac cells.

The spontaneous rhythmic activity of aggregates of embryonic chick heart cells was perturbed by the injection of single current pulses and periodic trains of current pulses. The regular and irregular dynamics produced by periodic stimulation were predicted theoretically from a mathematical analysis of the response to single pulses. Period-doubling bifurcations, in which the period of a regular oscillation doubles, were predicted theoretically and observed experimentally.

Animals↗

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

1. Small re-aggregates of cells dissociated from the ventricles of 7-day-old chick embryonic hearts beat spontaneously in low external potassium concentration (Ko = 1.3 mM) tissue culture medium. This activity was blocked by the addition of tetrodotoxin (TTX) or potassium ions to the external medium. 2. A two-micro-electrode voltage-clamp technique was used to analyse the subthreshold currents responsible for the pace-maker depolarization. 3. Voltage-clamp steps 6-10 sec in duration revealed a time-dependent current having first order kinetics. Its membrane potential range of steady-state activation was -90 to -60 mV. 4. The current kinetics were qualitatively similar to those of Hodgkin & Huxley (1952b) with a peak time constant of approximately 1 sec at V = -75 mV. The kinetics were independent of Ko. 5. The time-dependent current was attributed to gated membrane channels. The fully activated current-voltage (I-V) relation of the channels was determined from the ratio of the amplitudes of the time-dependent currents during and after voltage-clamp steps following the procedure of Noble & Tsien (1968). 6. The fully activated I-V relation displayed inward rectification with negative slope conductance at potentials more than 15 mV positive to its reversal potential. Changes of Ko shifted the I-V curve along the voltage axis like a potassium electrode. 7. The time-independent (background) current was obtained by subtracting the gated channel current from the steady-state I-V curve. This current also rectified in the inward direction. 8. The inwardly rectifying I-V relations were theoretically described by a channel having a row of ion-selective sites along which ions move in a single file (Hodgkin & Keynes, 1955), and a membrane-bound particle which blocked the channel in a voltage-dependent manner. 9. The relationship of the voltage-clamp results to spontaneous activity is discussed and comparisons are made with measurements from whole embryonic heart and other cardiac tissues.

Age Factors↗

Developmental changes in subthreshold pace-maker currents in chick embryonic heart cells.

1. Small re-aggregates of cells dissociated from the ventricles of 12-or 17-day-old chick embryonic hearts have beating properties in low potassium tissue culture medium which differ from re-aggregates prepared from 7-day-old hearts; 12-day preparations either beat with a slower rate than comparable-size 7-day preparations or they are quiescent; 17-day preparations usually do not beat. 2. A two-micro-electrode voltage-clamp technique was used to analyse the membrane currents in these preparations in the -120 to -40 mV potential range. 3. A potassium ion membrane current was measured in 12-day and 17-day preparations which was qualitatively similar to the potassium ion current measured in 7-day preparations (Clay & Shrier, 1981). It differed in that its amplitude was diminished in the ratio 1:0.2:0.03 over the 7-, 12- and 17-day sequence. Furthermore, its maximum time constant was 2 sec at both 12 and 17 days, as compared to 1 sec at 7 days, and its membrane potential range of activation was -80 to -70 mV at 12 and 17 days, as compared to -90 to -60 mV at 7 days. 4. The background current also changed with development, becoming less inward over the 7-, 12- and 17-day sequence. The voltage dependence of this change suggested that it was caused by a developmental decrease of the background sodium current. 5. The change in the background component is primarily responsible for the loss of automaticity over the 7-, 12-, and 17-day sequence.

Age Factors↗

Pacemaker currents in chick embryonic heart cells change with development.

The initial heartbeat of the chick embryo occurs shortly after the first day of incubation. The pacemaker of this beat originates in the region of the primitive heart destined to become sinoatrial tissue in the adult. Individual cells isolated from the atrial and ventricular portions of the embryonic heart are also capable of beating spontaneously at this stage. However, the intrinsic activity of these cells gradually diminishes from about day 7 until day 21 when the chick hatches. We have investigated these changes in automaticity by measuring membrane pacemaker currents with the voltage-clamp technique from aggregates of cells prepared from 7-, 12- and 17-day-old chick embryo cardiac ventricle. We report that there is a voltage and time dependent conductance at 7 days which is markedly reduced by 17 days. The reduction of this pacemaker current parallels the decrease of spontaneous activity in these preparations.

Age Factors↗

Junctional resistance and action potential delay between embryonic heart cell aggregates.

Spheroidal aggregates of embryonic chick ventricle cells were brought into contact and allowed to synchronize their spontaneous beats. Action potentials were recorded with both intracellular and extracellular electrodes. The degree of electrical interaction between the newly apposed aggregates was assessed by measuring the delay or latency (L) between the entrained action potentials, and by determining directly interaggregate coupling resistance (Rc) with injected current pulses. Aggregate size, contact area between the aggregates, and extracellular potassium concentration (Ko+) were important variables regulating the time-course of coupling. When these variables were controlled, L and Rc were found to be linearly related after beat synchrony was achieved. In 4.8 mM Ko+ L/Rc = 3.7 ms/M omega; in 1.3 mM Ko+ L/Rc = 10.1 ms/M omega. We conclude that action potential delay between heart cell aggregates can be related quantitatively to Rc.

Action Potentials↗

Herpes virus infection alters electrical parameters of heart cell aggregates.

The spontaneous beat of embryonic heart cell aggregates in culture grew gradually weaker and stopped about 18 h after inoculation with herpes simplex virus 1 (HSV-1). Before electrical activity ceased, maximal action potential upstroke velocity fell to about 20% of control values, whereas overshoot and plateau duration declined about 50%. Maximal diastolic potential was reduced by only about 10%. Eighteen hours after viral inoculation, specific membrane resistance and intercellular coupling were measured in quiescent aggregates with injected current pulses passed between two widely spaced intracellular electrodes. These parameters were unaltered as compared with control aggregates. However, pairs of infected aggregates brought into contact required 8 h to synchronize their beats; mock-inoculated aggregates coupled in less than 1 h. It is concluded that the cell surface alterations caused by HSV-1 infection specifically reduce both fast and slow inward currents and interfere with the formation of new nexal junctions.

Action Potentials↗