Heterogeneity of Intracellular Potassium Activity and Membrane Potential in Hypoxic Guinea Pig Ventricle

The relationship between membrane potential (Em) and the potassium equilibrium potential (EK) was investigated in hypoxic guinea pig papillary muscle. After more than 8 hours of hypoxia, cells with near normal Em (-86.2 +/- 0.9 mV) and action potentials were observed. However, the intracellular potassium concentration ([K+]i) based on chemical analysis and the assumption that potassium was homogeneously distributed was 41.8 +/- 4.3 mM; the apparent EK was -55.7 +/- 2.9 mV, significantly positive to Em. Measurements with potassium ion-selective microelectrodes revealed that prolonged hypoxia results in at least two populations of cells with different characteristics. The first population had an intracellular potassium activity (aiK) of 101.5 +/- 1.9 mM, and EK was 4.7 mV negative to Em. In contrast, EK was 33.4 +/- 1.3 mV negative to Em in the second population. These cells also exhibited a reduced sensitivity to changes in bath potassium, and calculations suggest aiK was about 18 mM. The existence of cell populations with a near normal and very low aiK can explain the intermediate value of [K+]i calculated assuming a homogenous potassium distribution. Cells with near normal Em and action potentials represent the population with near normal aiK. Hypoxia may also cause non-uniform changes in other cellular characteristics.