CARDIAC ELECTROPHYSIOLOGY: EFFECTS OF IONS AND DRUGS

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The cardiac Purkinje strand is a syncytium. The observed properties of any syncytium depend on both the membrane permeabilities and the interaction of the membrane current flows with the extracellular geometry. The present grant proposal builds on the previous five years of research in which the canine cardiac Purkinje strand was studied by various techniques including morphometric analysis, voltage clamp, extracellular ion selective microelectrodes, and impedance analysis. From these studies we have a characterization of the properties of the cell membrane as distorted by the extracellular space. One major aim of the present grant is to provide similar voltage clamp and impedance analysis of a new preparation, the acutely isolated canine cardiac Purkinje myocyte. It is hoped that a detailed voltage clamp analysis of this building block of the syncytium should provide the necessary missing link to allow us to accurately interpret our data from the intact Purkinje strands. Proposed studies of the dissociated cells include analysis of both plateau and diastolic delayed rectifiers, characterization of the Na/K pump current, and investigation of the effects of various pharmacologic agents on the steady state current-voltage relationship. A second aim of the present grant proposal is to continue our analysis of various membrane currents in the syncytial preparation. These currents include the Na/K pump current initiated by a period of rapid activity, the slowly inactivating TTX-sensitive "window current" and both plateau and diastolic delayed rectifiers. Some of the proposed experiments employ simultaneous measurements of both the membrane currents under voltage clamp and the extracellular [K]. This should provide additional insight into the importance of changes in cleft [K] in the interpretation of time dependent membrane currents. It is hoped that these experiments will provide an increase in our understanding of the control of both the action potential duration, and pacemaker activity in normal and pathologic conditions.