DISTINCT DOMAINS OF THE VOLTAGE-GATED K-BETA-1.3 BETA-SUBUNIT AFFECT VOLTAGE-DEPENDENT GATING( CHANNEL KV)

The Kv beta 1.3 subunit confers a voltage-dependent, partial inactivat ion (time constant = 5.76 +/- 0.14 ms at +50 mV), an enhanced slow ina ctivation, a hyperpolarizing shift in the activation midpoint, and an increase in the deactivation time constant of the Kv1.5 delayed rectif ier. Removal of the first 10 amino acids from Kv beta 1.3 eliminated t he effects on fast and slow inactivation but not the voltage shift in activation. Addition of the first 87 amino acids of Kv beta 1.3 to the amino terminus of Kv1.5 reconstituted fast and slow inactivation with out altering the midpoint of activation. Although an internal pore mut ation that alters quinidine block (V512A) did not affect Kv beta 1.3-m ediated inactivation, a mutation of the external mouth of the pore (R4 85Y) increased the extent of fast inactivation while preventing the en hancement of slow inactivation. These data suggest that 1) Kv beta 1.3 -mediated effects involve at least two distinct domains of this beta-s ubunit, 2) inactivation involves open channel block that is allosteric ally linked to the external pore, and 3) the Kv beta 1.3-induced shift in the activation midpoint is functionally distinct from inactivation .