The sinoatrial node (SAN) generates rhythmic electrical impulses that initiate each heartbeat. Recent high-resolution calcium imaging (single-cell level) discovered that the impulses emerge from noisy, heterogeneous signals, similar to that in neuronal networks in which a crucial property is an ability to store information, i.e., “Memory.” We hypothesized that memory encoded within SAN cells enables them to remember their previous action potential (AP) firing, and that this memory effect involves calcium stores (sarcoplasmic reticulum, SR). We isolated single SAN cells from rabbit hearts and perturbed them during 10 seconds by electrical currents of different shapes in current-clamp mode (perforated patch clamp). A major fraction of non-firing (dormant) cells continued AP firing after application of 3 Hz sine wave (9 of 17 cells, 52.9%) and white noise (22 of 75 cells, 29.3%). In the presence of cyclopiazonic acid (inhibiting SR calcium pump), the dormant cells could still be awakened to fire APs but always returned to their non-firing state after electrical stimulation, i.e., the memory effect disappeared. Applications of slowly changing current ramps (simulating tonic interactions in SAN tissue) did not evoke memory effects. These experimental results were reproduced in SAN cell model simulations. Thus, SAN cells can change their functional state (from non-firing to firing) by a temporal periodic stimulation rather than tonic interactions. The change occurs in response to signals at each SAN cell’s preferred resonance frequency (around 3 Hz) or white noise, simulating cell interactions within the heterogeneous environment of SAN tissue. This functional change involves the participation of the SR and can operate as memory within the SAN cellular network. This memory (information) encoded by the SR in the cells can be accessed (or read off) by neighboring cell clusters during their dynamic interactions (signal processing) within the network.
Okamura et al. (2026) studied this question.