Valinomycin inhibition of the electrical activity of mouse pancreatic beta-cells

The effect of the K-ionophore valinomycin (VAL) on the electrical activity of single mouse pancreatic beta-cells was measured using the glass micro-electrode technique. In the presence of 11.1 mM glucose, after 4 min of exposure to 10 nM VAL the spike activity was abolished, bursts became irregular and after 10 min the membrane hyperpolarized 4 mV. The electrical activity was completely blocked by 100 nM VAL within 3 min and the membrane hyperpolarization averaged 10 mV. The effect of VAL was irreversible. VAL (100 nM) also inhibited the electrical activity induced by 11.1 mM glucose plus 10 mM tetraethylammonium chloride (TEA), a specific blocker of the voltage sensitive PK. Total inhibition was observed 6-7 min after VAL addition and the cell hyperpolarized 14 mV. With the simultaneous application of 10 mM TEA and 100 microM quinine, a specific blocker of the [Ca2+]i-dependent PK, in the presence of 16.7 mM glucose, the membrane showed continuous activity and progressive depolarization from -45 to -5 mV within 23 min. The subsequent addition of 100 nM VAL also hyperpolarized the cell, with the membrane potential reaching -17 mV after 7 min. On the basis of these data, we suggest that VAL affects the glucose-dependent depolarization of the beta-cell membrane by increasing K+ permeability.