Ionic Mechanisms of Propagation in Cardiac Tissue: Roles of the Sodium and L-type Calcium Currents During Reduced Excitability and Decreased Gap Junction Coupling

Abstract

Abstract In cardiac tissue, reduced membrane excitability and reduced gap junction coupling both slow conduction velocity of the action potential. However, the ionic mechanisms of slow conduction for the two conditions are very different. We explored, using a multicellular theoretical fiber, the ionic mechanisms and functional role of the fast sodium current, I Na , and the L-type calcium current, I Ca(L) , during conduction slowing 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, reduced gap junction coupling caused a paradoxical increase in SF as conduction 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 third of control (from 54 to 17 cm/s) before failure occurred, whereas decreased coupling could reduce velocity to as low as 0.26 cm/s before block. 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 coupling was reduced. This phenomenon demonstrates that structural, nonmembrane factors can cause a switch of intrinsic membrane processes that support 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-dependent inactivation of I Ca(L) . The increase of safety factor during reduced coupling suggests a major involvement of uncoupling in stable slow conduction in infarcted myocardium, making microreentry possible. Reliance on I Ca(L) for this type of conduction suggests I Ca(L) as a possible target for antiarrhythmic drug therapy.