IONIC MECHANISMS OF PROPAGATION IN CARDIAC TISSUE - ROLES OF THE SODIUM AND L-TYPE CALCIUM CURRENTS DURING REDUCED EXCITABILITY AND DECREASED GAP JUNCTION COUPLING

In cardiac tissue, reduced membrane excitability and reduced gap junct ion coupling both slow conduction velocity of the action potential. Ho wever, the ionic mechanisms of slow conduction for the two conditions are Very different. We explored, using a multicellular theoretical fib er, the ionic mechanisms and functional role of the fast sodium curren t, I-Na, and the L-type calcium current, I-Ca(L), during conduction sl owing for the two fiber conditions. A safety factor for conduction (SF ) was formulated and computed for each condition. Reduced excitability caused a lower SF as conduction velocity decreased. In contrast, redu ced gap junction coupling caused a paradoxical increase in SF as condu ction velocity decreased. The opposite effect of the two conditions on SF was reflected in the minimum attainable conduction Velocity before failure: decreased excitability could reduce velocity to only one thi rd of control (from 54 to 17 cm/s) before failure occurred, whereas de creased coupling could reduce velocity to as low as 0.26 cm/s before b lock. Under normal conditions and conditions of reduced excitability, I-Ca(L) had a minimal effect on SF and on conduction. However, I-Ca(L) played a major role in sustaining conduction when intercellular coupl ing was reduced. This phenomenon demonstrates that structural, nonmemb rane factors can cause a switch of intrinsic membrane processes that s upport conduction. High intracellular calcium concentration, [Ca](i), lowered propagation safety and caused earlier block when intercellular coupling was reduced. [Ca](i) affected conduction via calcium-depende nt inactivation of I-Ca(L). The increase of safety factor during reduc ed coupling suggests a major involvement of uncoupling in stable slow conduction in infarcted myocardium, making microreentry possible. Reli ance on I-Ca(L) for this type of conduction suggests I-Ca(L) as a poss ible target for antiarrhythmic drug therapy.