INFLUENCE OF CLONED VOLTAGE-GATED K+ CHANNEL EXPRESSION ON ALANINE TRANSPORT, RB+ UPTAKE, AND CELL-VOLUME

Voltage-gated K+ channels are involved in regulation of action potential duration and in setting the resting membrane potential in nerve and muscle. To determine the effects of voltage-gated K+ channel expression on processes not associated with electrically excitable cells, we studied cell volume, membrane potential, Na+-K+-ATPase activity, and alanine transport after the stable expression of the Kv1.4 and Kv1.5 human K+ channels in Ltk- mouse fibroblasts (L-cells). The fast-activating noninactivating Kv1.5 channel, but not the rapidly inactivating Kvl.4 channel, prevented dexamethasone-induced increases in intracellular volume and inhibited Na+-K+-ATPase activity by 25%, as measured by Rb-86+ uptake. Alanine transport, measured separately by systems A and ASC, was lower in Kvl.5-expressing cells, indicating that the expression of this channel modified the Na+-dependent amino acid transport of both systems. Expression of the Kvl.4 channel did not alter alanine transport relative to wild-type or sham-transfected cells. The changes specific to Kvl.5 expression may be related to the resting membrane potential induced by this channel (-30 mV) in contrast to that measured in wild-type sham-transfected, or Kvl.4-transfected cells (-2 to 0 mV). Blocking of the Kvl.5 channel by 60 muM quinidine negated the effects of Kvl.5 expression on intracellular volume, Na+-K+-ATPase, and Na+-dependent alanine transport. These results indicate that delayed rectifier channels such as Kvl.5 can play a key role in the control of cell membrane potential, cell volume, Na+-K+-ATPase activity, and electrogenic alanine transport across the plasma membrane of electrically unexcitable cells.