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

¹Department of Physiology and ²Centre for Nonlinear Dynamics in Physiology and Medicine, McGill University, Montreal, Quebec, Canada; and ³Center of Physiological Medicine, Institute of Biophysics, Medical University Graz, Graz, Austria

Submitted 12 July 2004 ; accepted in final form 3 February 2005

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 Ba²⁺. 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 100 V/s vs. 10 V/s). On the basis of our voltage- and 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 Ca²⁺ current (I_Ca), three K⁺ currents (I_Ks, I_Kr, and I_K1), a background current, and a seal-leak current. I_Ca generates the slow upstroke, whereas I_Ks, I_Kr, and I_K1 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

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