Gap Junction Adaptation as a basis of cardiac memory - A computational Study

The phenomenon of cardiac memory refers to the property of cardiac tissue whereby the effect of an external electrical activation outlasts the duration of presentation of stimulus by significant margin. Several molecular mechanisms have been proposed in literature to explain the possible basis of this memory. Electrophysiological models of cardiac cells coupled by GJ conductances are studied. Simulations include cell pair models and grid models. Memory effect is shown in cell pair as a lasting change in phase difference between the oscillations of two autorhythmic type of cardiac cells. Memory effect is demonstrated in grid models also where an external current input presented for prolonged duration induces long term changes in activation pattern of the grid. These lasting changes are also reflected in computed Electrocardiogram.Physiological validity of the proposed mechanism of adaptation of GJs is also addressed. The proposed mechanism is inspired by results from learning and memory literature in neuroscience and comparing the same with the cardiac case. Just as neuronal signaling is mediated by synapses, cardiac cells electrically interact with each other via GJs. Activity-dependent adaptation of synaptic “strength” is generally considered an important biological substrate of learning and memory in the brain. Similarly, according to the proposed mechanism of GJ adaptation, the GJ conductance varies as a function of membrane voltages of the cells coupled by the GJ. But from biophysical literature, GJs are known to depend on junctional voltage between a pair of coupled cells. The link between biophysics of GJs and the proposed mechanism is explored. It is demonstrated with the help of a theoretical model of voltage-sensitive dynamics of GJ channel, followed up by simulation studies, that the proposed dynamics of GJs is compatible with biophysics of GJs.