Potassium channel alteration during hypoxia, metabolic stress and antihypertensive treatment in rat vascular tissue

The excitability of rat portal vein during hypoxia, metabolic stress and under exposure of the anti-hypertensive drug levcromakalim (BRL 38227) was studied using the single-cell voltage clamp technique. In single rat portal vein cells metabolic stress (no intracellular citric cycle intermediates in the pipette) and mild hypoxia (pO 2 = 80 mmHg) caused the slow development of an outward, glibenclamide-sensitive K current (IK ATP ). Exposure to levcromakalim further increased the magnitude of (IK ATP ), and in 40% of cells, this current showed only slight or no modification during the next 15 min. However, in the other 60% of cells, slow current oscillations of approximately 6-min cycle duration could be observed at the holding potential. These fluctuations were characterized by a high K + selectivity at their outward peaks and by an increase of the total input conductance and a reversal potential close to 0 mV in the troughs. Similarly, the reversal potential of the noise associated with current flow shifted from -80 mV at the peaks to 0 mV in the troughs. All levcromakalim-induced current changes, the subsequent oscillations and associated increased input conductance, were inhibited by the sulfonurea receptor agonist glibenclamide. This altered selectivity of the potassium channel (K ATP ) changes the excitation pattern of the vascular tissue and prevents tissue protection.