The proposed research will examine the basis for membrane potential (Em) in the atrio-ventricular node (AVN) of rabbit heart. Em in the AVN is lower than in atrium, ventricle or Purkinje fiber and is relatively insensitive to changes in extracellular potassium activity. These findings have been explained by postulating that intracellular chloride activity is greater than required by passive distribution at Em and that PCl/PK, the ratio of chloride permeability to potassium permeability, is relatively high. However, neither intracellular chloride activity nor PCl/PK are known. Alternatively, as I have postulated here, the intracellular potassium activity may be lower than in other cardiac tissues, and it may be strongly dependent on extracellular potassium activity. The experiments proposed will critically test these two hypotheses. Potassium ion-selective microelectrodes and chloride ion-selective microelectrodes will be used to measure the intracellular activities of potassium and chloride directly. PCl/PK will be calculated. The relationships between Em and both extracellular potassium and chloride activities will be determined. The control of intracellular potassium activity will be studied by varying its extracellular activity. The control of intracellular chloride activity will be studied by varying the extracellular activities of potassium and chloride. These experiments will lead to an understanding of the basis of Em in AVN and will provide the baseline data necessary to understand more complex electrical, pharmacological, and pathological events.
