MODULATING L-TYPE CALCIUM CURRENT AFFECTS DISCONTINUOUS CARDIAC ACTION-POTENTIAL CONDUCTION

We have used pairs of cardiac cells (i.e., one real guinea pig ventric ular cell and a real-time simulation of a numerical model of a guinea pig ventricular cell) to evaluate the effects on action potential cond uction of a variable coupling conductance in combination with agents t hat either increase or decrease the magnitude of the L-type calcium cu rrent. For the cell pairs studied, we applied a direct repetitive stim ulation to the real cell, making it the ''leader'' cell of the cell pa ir. We have demonstrated that significant delays in action potential c onduction for a cell pair can occur either with a decreased value of c oupling conductance or with an asymmetry in size such that the followe r cell is larger than the leader cell. In both conditions we have show n that isoproterenol, applied to the real cell at very low concentrati ons, can reversibly decrease the critical coupling conductance (below which action potential conduction fails) for a cell pair with fixed ce ll sizes, or, for a fixed value of coupling conductance, increase the maximum allowable asymmetry in cell size for successful conduction. Fo r either of these effects, we were able to show that treatment of the real cell with BayK 8644, which more specifically increases the magnit ude of the L-type calcium current, was able to mimic the actions of is oproterenol. Treatment of the leader cell of the cell pair (the real c ell) with nifedipine, which selectively lowers the magnitude of the L- type calcium current, had effects opposite those of isoproterenol or B ayK 8644. The actions of nifedipine, isoproterenol, and BayK 8644 are all limited to conditions in which the conduction delay is on the orde r of 5 ms or more, whether this delay is caused by limited coupling co nductance or by asymmetry in size of the cells. This limitation is con sistent with the time course of the L-type calcium current and suggest s that the effects of calcium channel blockers or beta-adrenergic bloc king drugs, in addition to being selective for regions of the heart th at depend on the L-type calcium current for the upstroke of the action potential, would also be somewhat selective for regions of the heart that have discontinuous conduction, either normally or because of some pathological condition.