The effects of intercellular coupling conductance on the activity of two electrically coupled isolated rabbit sinoatrial nodal cells were investigated. A computer-controlled version of the "coupling clamp" technique was used in which isolated sinoatrial nodal cells, not physically in contact with each other, were electrically coupled at various values of ohmic coupling conductance, mimicking the effects of mutual interaction by electrical coupling through gap junctional channels. We demonstrate the existence of four types of electrical behavior of coupled spontaneously active cells. As the coupling conductance is progressively increased, the cells exhibit: (a) independent pacemaking at low coupling conductances, (b) complex dynamics of activity with mutual interactions, (c) entrainment of action potential frequency at a 1:1 ratio with different action potential waveforms, and (d) entrainment of action potentials at the same frequency of activation and virtually identical action potential waveforms. The critical value of coupling conductance required for 1:1 frequency entrainment was �0.5 nS in each of the five cell pairs studied. The common interbeat interval at a relatively high coupling conductance (10 nS), which is sufficient to produce entrainment of frequency and also identical action potential waveforms, is determined most by the intrinsically faster pacemaker cell and it can be predicted from the diastolic depolarization times of both cells. Evidence is provided that, at low coupling conductances, mutual pacemaker synchronization results mainly from the phase-resetting effects of the action potential of one cell on the depolarization phase of the other. At high coupling conductances, the tonic, diastolic interactions become more important. In the sinoatrial (SA) 1 node synchronization of the actia regular rate. The mechanisms by which cells with difvation of electrically coupled, spontaneously pacing ferent intrinsic rates of automaticity maintain this syncells is a required attribute of normal action potential chronization has been the subject of numerous studies using a variety of experimental and model systems. initiation. Individual isolated SA nodal cells display a Several experimental approaches have been used to large variety in action potential waveforms (Nakayama study the electrical interactions between cardiac cells as et Jongsma, 1986, 1995). Morea function of intercellular conductance without the over, individual cells may have irregular firing patterns, with a varying cycle length (Opthof, 1988; Wilders and complexity of a multidimensional syncytium. Studies using thin SA node strips (Jalife, 1984; Delmar et al., Jongsma, 1993), which is most likely due to differences 1986), with the central region of the strip sealed off in in the composition of membrane currents (Nathan, 1986;Honjo et al., 1996). For the SA node to maintain a compartment containing either ion-free sucrose solua stable and regular discharge pattern, individual cells tion or Tyrode solution containing heptanol, sh...
The anisotropy that normally exists in the myocardium may be either enhanced in peri-infarction zones by loss of lateral cell connections or reduced by redistribution of gap junctions. To test how the degree of anisotropy affects the development of ectopic focal activity, we carried out computer simulations in which a model of an ectopic focus is incorporated as the central element of a two-dimensional sheet of ventricular cells. At low values of intercellular coupling conductance (G c ), the focus region is spontaneously active, but the limited intercellular current flow inhibits propagation. At high G c , automaticity is suppressed by the loading effects of the surrounding cells. At intermediate G c , the ectopic activity may propagate into the sheet. In the case of isotropic coupling, the minimum size of the focus region for propagation to occur (in terms of number of collaborating cells within the focus) is as small as approximately ten cells, and this number decreases with increasing anisotropy. Thus, the presence of anisotropy facilitates the development of ectopic focal activity. We conclude that the remodeling that occurs in peri-infarction zones may create a substrate that either facilitates (enhanced anisotropy) or inhibits (reduced anisotropy) the development of cardiac arrhythmias associated with ectopic focal activity.
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