Ionic currents involved in shock-induced nonlinear changes in transmembrane potential responses of single cardiac...

An exhaustive characterization of how an isolated cardiac cell responds to applied electric fields could serve as an important groundwork for understanding responses of more complex higher order systems. Field stimulation of single cardiac cells during the early plateau of the action potential results in a nonuniform change in transmembrane potential (Vm) across the cell length that is more heavily weighted in the negative direction. These negatively shifted Vm responses are not replicated theoretically using present day membrane models. The goal of this study was to explore the membrane currents involved in the field responses during the plateau by selectively blocking various ion channels. Enzymatically isolated single guinea pig cells were stimulated with uniform field S1-S2 pulses, and the transmembrane potential responses were optically recorded from several sites along the cell length to assess the drug effect. We used nine different pharmacological agents to manipulate the conductance of major cardiac ion channels of which only barium (Ba2+) altered the transmembrane potential responses. At 50 microM Ba2+, which specifically blocks inwardly rectifying current I(K1), the negative shift in Vm responses was accentuated. At 1 mM Ba2+ , which blocks both I(K1) and sustained plateau current I(Kp), the negative shift diminished. However, 1 mM Ba2+ also depolarized the cells, and depressed or completely eliminated the action potential. Based on these results we conclude that I(K1) contributes to field-induced responses during the plateau stimulation by passing a net inward current, which when blocked accentuates the negative shift in the Vm responses. A conclusive role of I(Kp) could not be demonstrated because of confounding changes in membrane potential. However, from our results it remains as the most viable candidate for the elusive current that contributes a net outward current to produce negatively weighted Vm responses during plateau stimulation and warrants further investigation.