Potential-dependent block of human delayed rectifier K+ channels by internal Na+

Abstract

The delayed rectifier K+ currents in differentiated human SH-SY5Y neuroblastoma cells were characterized with tight-seal recording techniques. Activation and inactivation parameters were measured. At high positive potentials, the current showed a marked rectification, causing a region of negative slope conductance in the current vs. potential curve. The rectification depended markedly on the pipette Na+ concentration. Without Na+, no rectification was observed, whereas with high Na+ (20-60 mM), a marked rectification was always observed. Tail current measurements showed a fast ( < 400 microseconds) block of K+ currents in the presence of internal Na+. With 60 mM Na+ in the pipette 8% of the K+ current was blocked at 0 mV, 27% at +20 mV, and 82% at +100 mV. Similar degrees of block were often seen with 30 mM Na+ in the pipette. The submembrane Na+ concentration in intact cells was estimated, on the basis of the reversal of Na+ current, to be approximately 15 mM. Single-channel K+ currents, in the cell-attached configuration, showed a conductance of approximately 20 pS at 40-60 mV above rest but showed rectification at high potentials.