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Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 α-subunits

1998; American Physical Society; Volume: 274; Issue: 6 Linguagem: Inglês

10.1152/ajpcell.1998.274.6.c1501

1522-1563

James Kramer, Marc Post, Arthur Brown, Glenn E. Kirsch,

Coordination Chemistry and Organometallics

We have determined the effects of coexpression of Kv2.1 with electrically silent Kv5.1 or Kv6.1 α-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 α-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 α-subunits that when coassembled with Kv2.1 can modulate gating in a physiologically relevant manner.