Properties of voltage-gated K+ currents expressed in Xenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1.
Two similar mouse Shaker-like K+ channel genes, mKv1.1 and mKv1.2, have been shown to form heteromultimers in vivo. The predicted amino acid sequence of each channel is nearly identical in mice, rats and humans, suggesting that each has been highly conserved evolutionarily. Here we report the biophysical and pharmacological properties of each channel when expressed alone or when coexpressed in Xenopus oocytes. The voltage sensitivities of activation were similar for both, but the voltages at which the K+ conductances were half-maximal (V1/2) were -37 mV and -27 mV for mKv1.1 and mKv1.2 respectively. Both displayed voltage-dependent, but incomplete, inactivation following a prepulse with mKv1.2 showing the greater degree of inactivation. For mKv1.1, the onset and recovery from inactivation could be described by single, slow time constants (2-4 s), whereas for mKv1.2 the onset and recovery from inactivation displayed a second, faster time constant (< 400 ms). Using a mutant mKv1.1 that is 100-fold less sensitive to dendrotoxin-I than mKv1.1, we demonstrate that this mutant mKv1.1 and wild-type mKv1.2 subunits can form heteromultimeric channels. With some exceptions, of unknown significance, the biophysical properties of the heteromultimeric channels formed by wild-type mKv1.1 and mKv1.2 subunits were intermediate between those of mKv1.1 and mKv1.2 homomultimers, but quantitatively more similar to the more abundant subunit.
Hopkins
W F
WF
Geriatric Research Education and Clinical Center (182-B), Veterans Affairs Medical Center, Seattle, WA 98108.
Allen
M L
ML
Houamed
K M
KM
Tempel
B L
BL
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D004546:Elapid Venoms / Q000378:metabolism*; D004594:Electrophysiology; D015870:Gene Expression; D015640:Ion Channel Gating; D007700:Kinetics; D051379:Mice / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D004546:Elapid Venoms; D015345:Oligonucleotide Probes; D015221:Potassium Channels; C020273:dendrotoxin