A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits.
Voltage-gated potassium channel beta subunits are cytoplasmic proteins that co-purify with the pore-forming alpha subunits. One of these subunits, Kv beta 1 from rat brain, was previously demonstrated to increase the rate of inactivation of Kv1.1 and Kv1.4 when co-expressed in Xenopus oocytes. We have cloned and characterized a novel voltage-gated K+ channel beta subunit. The cDNA, designated Kv beta 3, has a 408-amino acid open reading frame. It possesses a unique 79-amino acid N-terminal leader, but is identical with rat Kv beta 1 over the 329 C-terminal amino acids. The Kv beta 3 transcript was found in many tissues, but was most abundant in aorta and left ventricle of the heart. Co-expression of Kv beta 3 with K+ channel alpha subunits shows that this beta subunit can increase the rate of inactivation from 4- to 7-fold in a Kv1.4 or Shaker B channel. Kv beta 3 had no effect on Kv1.1, unlike Kv beta 1 which can increase rate of inactivation of this alpha subunit more than 100-fold. Other kinetic parameters were unaffected. This study shows that voltage-gated K+ channel beta subunits are present outside the central nervous system, and that at least one member of this family selectively modulates inactivation of K+ channel alpha subunits.
Morales
M J
MJ
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Castellino
R C
RC
Crews
A L
AL
Rasmusson
R L
RL
Strauss
H C
HC
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D017931:DNA Primers; D005289:Ferrets; D015870:Gene Expression; D006352:Heart Ventricles; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D046911:Macromolecular Substances; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D017931:DNA Primers; C494839:Kcnab1 protein, rat; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D046911:Macromolecular Substances; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012333:RNA, Messenger