Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits.
We have determined the effects of coexpression of Kv2.1 with electrically silent Kv5.1 or Kv6.1 alpha-subunits in Xenopus oocytes on channel gating. Kv2.1/5.1 selectively accelerated the rate ofinactivation 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 alsoslowed 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 alpha-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 alpha-subunits that when coassembled with Kv2.1 can modulate gating in a physiologically relevant manner.
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44109, USA.
J W
JW
Kramer
M A
MA
Post
A M
AM
Brown
G E
GE
Kirsch
D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D015870:Gene Expression; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels; D014162:Transfection; D014981:Xenopus
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels