Analysis of field-induced transmembrane potential responses of single cardiac cells in terms of active and passive components

Abstract

Field-induced transmembrane potential (V/sub m/) responses of cardiac cells have complex spatiotemporal variation. We show that these responses can be decomposed into simpler components that facilitate their understanding. Enzymatically isolated guinea pig cardiac cells were stained with /spl sim/50 /spl mu/M voltage sensitive dye di-8-ANEPPS, and stimulated along their longitudinal axes using a pair of S1 (5 ms) and S2 (10 ms) uniform field pulses (S1-S2=20 ms). The V/sub m/ responses recorded using a multisite optical mapping system were decomposed into a differential-mode component V/sub md/ and a common mode component (V/sub mc/). The V/sub md/ varies linearly along the cell length, and describes the passive component of the field responses. The V/sub mc/ is uniform along the cell length, and describes the active component. The V/sub mc/ arises from an imbalance in membrane currents along the cell length, and is depolarizing at rest and hyperpolarizing during the plateau. It has been shown previously that a model cell with dynamic Luo-Rudy) membrane currents fails to reproduce the hyperpolarizing V/sub m/ responses during the plateau, and a hypothetical outwardly rectifying current I/sub a/ has been proposed to resolve the discrepancy. However, the true ion channel basis of I/sub a/ has not been resolved. Using pharmacological interventions we dissect the membrane currents involved during the plateau responses, and suggest that the sustained plateau current (I/sub kp/) is most likely the ion channel correlate of I/sub a/.