Model clamp: a computer tool to probe action potential transfer between cardiac cells

Abstract

-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 the computer-controlled "model clamp" technique, 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. In courses on cardiac electrophysiology, the model clamp system provides a useful computer tool to probe action potential transfer between cardiac cells. It can be used to assess alterations in the critical value of coupling conductance required for action potential transfer from a real ventricular cell to the Luo-Rudy model ventricular cell upon exposure of the real cell to, e.g., noradrenaline.Keywords -Heart, electrophysiology, ventricular cells, action potentials, gap junctions, computer simulations I. INTRODUCTIONCardiac activation patterns depend on the multidimensional distribution of cellular membrane properties and intercellular electrical coupling. The anatomical complexity of cardiac tissue, however, makes it difficult, if not impossible, to use tissue experiments to investigate how cellular properties and intercellular coupling influence the observed experimental behavior. Several experimental approaches have been made to study electrical interactions between cardiac cells as a function of intercellular conductance without the complexity of a multidimensional syncytium. In the early nineties, Joyner and coworkers introduced the "coupling clamp" system in which two isolated cells not in physical contact with each other can be electrically coupled at any desired value of intercellular conductance by means of an external circuit that continuously applies time-varying currents to each cell with a sign and magnitude that would have been present if the cells would have been physically coupled. The coupling clamp system allows the rapid independent measurement of the intrinsic cellular properties and then the analysis of the effects of a wide range of intercellular conductance values on the electrical behavior of the cells. At any time during the experiment, the measurements of intrinsic cellular properties can be repeated by temporarily uncoupling the cells.In their initial paper [1], Joyner and coworkers documented this "coupling clamp" technique and showed that coupling an isolated rabbit ventricular cell to a passive resistance-andcapacitance (RC) circuit representing an inexcitable cell with a normal resting potential, produced...