Effects of Kv1.2 intracellular regions on activation of Kv2.1 channels.
Depolarizing voltage steps activate voltage-dependent K(+) (Kv) channels by moving the voltage sensor, which triggers a coupling reaction leading to the opening of the pore. We constructed chimeric channels in which intracellular regions of slowly activating Kv2.1 channels were replaced by respective regions of rapidly activating Kv1.2 channels. Substitution of either the N-terminus, S4-S5 linker, or C-terminus generated chimeric Kv2.1/1.2 channels with a paradoxically slow and approximately exponential activation time course consisting of a fast and a slow component. Using combined chimeras, each of these Kv1.2 regions further slowed activation at the voltage of 0 mV, irrespective of the nature of the other two regions, whereas at the voltage of 40 mV both slowing and accelerating effects were observed. These results suggest voltage-dependent interactions of the three intracellular regions. This observation was quantified by double-mutant cycle analysis. It is concluded that interactions between N-terminus, S4-S5 linker, and/or C-terminus modulate the activation time course of Kv2.1 channels and that part of these interactions is voltage dependent.
Scholle
Annette
A
Institut für Physiologie II, Friedrich-Schiller-Universität, 07740 Jena, Germany.
Zimmer
Thomas
T
Koopmann
Rolf
R
Engeland
Birgit
B
Pongs
Olaf
O
Benndorf
Klaus
K
D000818:Animals; D002478:Cells, Cultured; D042541:Intracellular Space / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D051663:Kv1.2 Potassium Channel; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D051669:Shab Potassium Channels; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D051663:Kv1.2 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051669:Shab Potassium Channels