PROPERTIES OF VOLTAGE-GATED K-BINDING SITE IN MKV1.1( CURRENTS EXPRESSED IN XENOPUS OOCYTES BY MKV1.1, MKV1.2 AND THEIR HETEROMULTIMERS AS REVEALED BY MUTAGENESIS OF THE DENDROTOXIN)

Two similar mouse Shaker-Like K+ channel genes, mKv1.1 and mKv1.2, hav e 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 chann el when expressed alone or when coexpressed in Xenopus oocytes. The vo ltage sensitivities of activation were similar for both, but the volta ges at which the K+ conductances were half-maximal (V-1/2) were -37 mV and -27 mV for mKv1.1 and mKv1.2 respectively. Both displayed voltage -dependent, but incomplete, inactivation following a prepulse with mKv 1.2 showing thp 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 ina ctivation displayed a second, faster time constant (< 400 ms). Using a mutant mKv1.1 that is 100-fold less sensitive to dendrotoxin-I than m Kv1.1, we demonstrate that this mutant mKv1.1 and wild-type mKv1.2 sub units can form heteromultimeric channels. With some exceptions, of unk nown significance, the biophysical properties of the heteromultimeric channels formed by wild-type mKv1.1 and mKv1.2 subunits were intermedi ate between those of mKv1.1 and mKv1.2 homomultimers, but quantitative ly more similar to the more abundant subunit.