| Abstract: | We havedetermined the effects of coexpression of Kv2.1 with electricallysilent Kv5.1 or Kv6.1  -subunits inXenopus oocytes on channel gating.Kv2.1/5.1 selectively accelerated the rate of inactivation atintermediate potentials ( 30 to 0 mV), without affecting the rateat strong depolarization (0 to +40 mV), and markedly accelerated therate of cumulative inactivation evoked by high-frequency trains ofshort pulses. Kv5.1 coexpression also slowed deactivation of Kv2.1. Incontrast, Kv6.1 was much less effective in speeding inactivation atintermediate potentials, had a slowing effect on inactivation at strongdepolarizations, and had no effect on cumulative inactivation. Kv6.1,however, had profound effects on activation, including a negative shift of the steady-state activation curve and marked slowing of deactivation tail currents. Support for the notion that the Kv5.1's effects stemfrom coassembly of -subunits into heteromeric channels was obtainedfrom biochemical evidence of protein-protein interaction andsingle-channel measurements that showed heterogeneity in unitary conductance. Our results show that Kv5.1 and Kv6.1 function as regulatory -subunits that when coassembled with Kv2.1 can modulate gating in a physiologically relevant manner. |
