Ionic mechanisms of electronic inhibition and concealed conduction in rabbit atrioventricular nodal myocytes.

Abstract

The term "concealed conduction" is used in electrocardiography when a proximal (atrial or ventricular) impulse penetrates the atrioventricular (AV) node but fails to traverse it completely. Its penetration into the node is inferred by its after effects on the propagation of succeeding impulses. Concealed AV nodal conduction is a well-established phenomenon, but its precise cellular and subcellular mechanisms are unknown. It has been suggested that concealed conduction results from a transient impairment of excitability caused by the subthreshold depolarization (ie, electrotonic inhibition) that is elicited downstream of the site of block. We studied the ionic mechanism of electrotonic inhibition and concealed conduction in single myocytes isolated from the rabbit AV node. Cells were paced using just-threshold current pulses delivered at a constant (basic) cycle length of 1 second. Appropriately timed interpolation of a conditioning pulse of depolarizing but subthreshold current led to failure of the subsequent, previously successful activation. The ability of the subthreshold response to inhibit subsequent excitation was increased when the interval between the conditioning and succeeding pulses was shortened, when the amplitude of the conditioning pulse was increased, or when the inward sodium current was blocked by superfusion with tetrodotoxin (30 microM). Voltage clamp analysis demonstrated that electrotonic inhibition results from partial inactivation of the transient calcium current (ICa.T). Similar results were obtained using a mathematical model (Hodgkin-Huxley type) of the AV nodal myocyte. Additional simulations in a linear array of AV nodal cells showed that when a premature impulse fails to traverse the AV node, the subthreshold depolarization elicited downstream of the site of block may lead to a transient reduction of excitability with consequent delay or block of the succeeding impulse. The overall data strongly suggest that some of the electrocardiographic manifestations of concealed AV conduction are the result of electrotonic inhibition of excitability secondary to a transient decrease in ICa.T.