Abstract: | The Kv 1.3 subunit confers a voltage-dependent, partialinactivation (time constant = 5.76 ± 0.14 ms at +50 mV), anenhanced slow inactivation, a hyperpolarizing shift in the activationmidpoint, and an increase in the deactivation time constant of theKv1.5 delayed rectifier. Removal of the first 10 amino acids fromKv 1.3 eliminated the effects on fast and slow inactivation but notthe voltage shift in activation. Addition of the first 87 amino acids of Kv 1.3 to the amino terminus of Kv1.5 reconstituted fast and slowinactivation without altering the midpoint of activation. Although aninternal pore mutation that alters quinidine block (V512A) did notaffect Kv 1.3-mediated inactivation, a mutation of the external mouthof the pore (R485Y) increased the extent of fast inactivation whilepreventing the enhancement of slow inactivation. These data suggestthat 1) Kv 1.3-mediated effects involve at least two distinct domains of this -subunit,2) inactivation involves openchannel block that is allosterically linked to the external pore, and3) the Kv 1.3-induced shift in theactivation midpoint is functionally distinct from inactivation. |