A small domain in the N terminus of the regulatory alpha-subunit Kv2.3 modulates Kv2.1 potassium channel gating

Recent work has demonstrated the existence of regulatory K+ channel alpha-s ubunits that are electrically silent but capable of forming heterotetramers with other pore-forming subunits to modify their function. We have investi gated the molecular determinant of the modulatory effects of Kv2.3, a silen t K+ channel alpha-subunit specific of brain. This subunit induces on Kv2.1 channels a marked deceleration of activation, inactivation, and closing ki netics. We constructed chimeras of the Kv2.1 and Kv2.3 proteins and analyze d the K+ currents resulting from the coexpression of the chimeras with Kv2. 1. The data indicate that a region of 59 amino acids in the N terminus, adj acent to the first transmembrane segment, is the major structural element r esponsible for the regulatory function of Kv2.3. The sequence of this domai n of Kv2.3 is highly divergent compared with the same region in the other c hannels of the Kv2 family. Replacement of the regulatory fragment of Kv2.3 by the equivalent of Kv2.1 leads to loss of modulatory function, whereas ga in of modulatory function is observed when the Kv2.3 fragment is transferre d to Kv2.1. Thus, this study identifies a N-terminus domain involved in Kv2 .1 channel gating and in the modulation of this channel by a regulatory alp ha-subunit.