Effects of quinine and apamin on the calcium-dependent potassium permeability of mammalian hepatocytes and red cells

Abstract

1. K-sensitive electrodes placed in the extracellular fluid have been used to show that ATP and noradrenaline cause a rapid loss of up to 10% of the K content of isolated guinea-pig hepatocytes. 2. The hypothesis tha this response is a consequence of a rise in the K permeability of the hepatocyte membrane triggered by an increase in cytosolic Ca is supported by the finding that the divalent cation ionophore A23187 also initiated K loss, in this instance of up to 20-25% of the amount in the cells. 3. Under similar conditions A23187 caused a transient increase, followed by a larger decrease, in the 45Ca content of guinea-pig hepatocytes equilibrated with this isotope. The decrease alone was seen with ATP and noradrenaline. 4. Quinine (1 mM) and the bee venom neurotoxin apamin (10 nM) greatly reduced the effect of ATP, noradrenaline and A23187 on K content without affecting the changes in 45Ca movement. 5. Apamin (10 nM) also abolished the increase in 42K efflux which follows the application of the alpha-adrenoceptor agonist amidephrine to rabbit liver slices; the concurrent rises in 45Ca efflux and glucose release were unaffected. 6. It was concluded that quinine and apamin are able to block either the Ca-dependent K channels present in guinea-pig and rabbit liver cell membranes or the mechanism that controls them. 7. Surprisingly, rat hepatocytes took up rather than lost K when treated with the concentrations of ATP, noradrenaline or A23187 that initiated K loss from guinea-pig cells. This response was greatly reduced by ouabain. 8. Application of large concentrations of A23187 to rat hepatocytes caused K loss associated with cell death. 9. The influence of apamin (10-1000 nM) and quinine (200-1000 micro M) on the Ca-dependent K permeability of red blood cells and ghosts was also studied. Apamin was without effect even when applied to both sides of the ghost membrane, whereas quinine caused inhibition, as reported by others. 10. The results suggest that Ca-dependent K channels or carriers are present in the membranes of liver cells of the guinea-pig and rabbit, but are either lacking or inactive in rat liver. The finding that apamin blocks this mechanism in hepatocytes but not in erythrocytes may mean that the channels differ in these cells.