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-subunits
Department of Physiology and Biophysics, Rammelkamp Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109
We have
determined the effects of coexpression of Kv2.1 with electrically
silent Kv5.1 or Kv6.1
-subunits in
Xenopus oocytes on channel gating.
Kv2.1/5.1 selectively accelerated the rate of inactivation at
intermediate potentials (
30 to 0 mV), without affecting the rate
at strong depolarization (0 to +40 mV), and markedly accelerated the
rate of cumulative inactivation evoked by high-frequency trains of
short pulses. Kv5.1 coexpression also slowed deactivation of Kv2.1. In
contrast, Kv6.1 was much less effective in speeding inactivation at
intermediate potentials, had a slowing effect on inactivation at strong
depolarizations, 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 stem
from coassembly of
-subunits into heteromeric channels was obtained
from biochemical evidence of protein-protein interaction and
single-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.
rat brain; Xenopus oocytes; delayed rectifier; DRK1; IK8; K13
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