Heteromeric assembly of Kv2.1 with Kv9.3: Effect on the state dependence of inactivation

Modulatory ar-subunits of Ky channels remain electrically silent after homo meric expression. Their interactions with Kv2 alpha-subunits via the amino- terminal domain promote the assembly of heteromeric functional channels. Th e kinetic features of these heteromers differ from those of Kv2 homomers, s uggesting a distinct role in electrical signaling. This study investigates biophysical properties of channels emerging from the coexpression of Kv2.1 with the modulatory alpha-subunit Kv9.3. Changes relative to homomeric Kv2. 1 concern activation, deactivation, inactivation, and recovery from inactiv ation. A detailed description of Kv2.1/Kv9.3 inactivation is presented. Kv2 .1/Kv9.3 heteromers inactivate in a fast and complete fashion from intermed iate closed states, but. in a slow and incomplete manner from open states. Intermediate closed states of channel gating can be approached through part ial activation or deactivation, according to a proposed qualitative model. These transitions are rate-limiting for Kv2.1/Kv9.3 inactivation. Finally, based on the kinetic description, we propose a putative function for Kv2.1/ Kv9.3 heteromers in rat heart.