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-subunits that are electrically silent but capable of forming heterotetramers with other pore-forming subunits to modify their function. We have investigated the molecular determinant of the modulatory effects of Kv2.3, a silent K(+) channel alpha-subunit specific of brain. This subunit induces on Kv2.1 channels a marked deceleration of activation, inactivation, and closing kinetics. We constructed chimeras of the Kv2.1 and Kv2.3 proteins and analyzed 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, adjacent to the first transmembrane segment, is the major structural element responsible for the regulatory function of Kv2.3. The sequence of this domain of Kv2.3 is highly divergent compared with the same region in the other channels 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 gain of modulatory function is observed when the Kv2.3 fragment is transferred 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 alpha-subunit.
Chiara
M D
MD
Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, E-41009 Sevilla, Spain.
Monje
F
F
Castellano
A
A
López-Barneo
J
J
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D051668:Delayed Rectifier Potassium Channels; D015640:Ion Channel Gating; D007700:Kinetics; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology; D051669:Shab Potassium Channels
D051668:Delayed Rectifier Potassium Channels; C120777:KCNV1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels