Electrical interactions between cardiac cells studied with coupling clamp and model clamp

In the early nineties, Joyner and coworkers introduced the "coupling clamp" technique in which an isolated cardiac cell can be electrically coupled to either another isolated cardiac cell or to an analog model cell (RC circuit). In brief, an amplifier system does a continuous analog computation of the current that would be flowing between the two cells if there had been an intercellular coupling conductance G_c, and then provides current inputs to the cells accordingly. Building on this concept, we developed a computer-controlled coupling clamp system, as well as a "model clamp" system, in which an isolated cardiac cell is dynamically coupled in real time to a comprehensive mathematical cell model (e.g., the phase-2 Luo-Rudy model). With this system we have the ability to vary coupling conductance, effective size of both model cell and real cell, and intrinsic cellular properties of the model cell. We used the digital coupling clamp to study the synchronization of two sinoatrial nodal cells, and found that the critical value of coupling conductance required for 1:1 frequency entrainment was <0.5 nS, whereas G_c ≥10 nS was required for waveform entrainment. We used the model clamp to assess alterations in the critical value of coupling conductance required for action potential conduction from a real ventricular cell to the Luo-Rudy model ventricular cell when the real cell was exposed to a solution mimicking acute ischemia. We observed that conduction was inhibited in the standard 'ischemic' solution, but facilitated when noradrenaline was added to the 'ischemic' solution.