Distinct domains of the voltage-gated K+ channel Kv beta 1.3 beta-subunit affect voltage-dependent gating.
The Kvbeta1.3 subunit confers a voltage-dependent, partial inactivation (time constant = 5.76 +/- 0.14 ms at +50 mV), an enhanced slow inactivation, a hyperpolarizing shift in the activation midpoint, and an increase in the deactivation time constant of the Kv1.5 delayed rectifier. Removal of the first 10 amino acids from Kvbeta1.3 eliminated the effects on fast and slow inactivation but not the voltage shift in activation. Addition of the first 87 amino acids of Kvbeta1.3 to the amino terminus of Kv1.5 reconstituted fast and slow inactivation without altering the midpoint of activation. Although an internal pore mutation that alters quinidine block (V512A) did not affect Kvbeta1.3-mediated inactivation, a mutation of the external mouth of the pore (R485Y) increased the extent of fast inactivation while preventing the enhancement of slow inactivation. These data suggest that 1) Kvbeta1.3-mediated effects involve at least two distinct domains of this beta-subunit, 2) inactivation involves open channel block that is allosterically linked to the external pore, and 3) the Kvbeta1.3-induced shift in the activation midpoint is functionally distinct from inactivation.
Uebele
V N
VN
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
England
S K
SK
Gallagher
D J
DJ
Snyders
D J
DJ
Bennett
P B
PB
Tamkun
M M
MM
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D016296:Mutagenesis; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011802:Quinidine / Q000494:pharmacology; D014981:Xenopus
D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011802:Quinidine; D011188:Potassium