KChAP/Kvbeta1.2 interactions and their effects on cardiac Kv channel expression.
KChAP and voltage-dependent K+ (Kv) beta-subunits are two different types of cytoplasmic proteins that interact with Kv channels. KChAP acts as a chaperone for Kv2.1 and Kv4.3 channels. It also binds to Kv1.x channels but, with the exception of Kv1.3, does not increase Kv1.x currents. Kvbeta-subunits are assembled with Kv1.x channels; they exhibit "chaperone-like" behavior and change gating properties. In addition, KChAP and Kvbeta-subunits interact with each other. Here we examine the consequences of this interaction on Kv currents in Xenopus oocytes injected with different combinations of cRNAs, including Kvbeta1.2, KChAP, and either Kv1.4, Kv1.5, Kv2.1, or Kv4.3. We found that KChAP attenuated the depression of Kv1.5 currents produced by Kvbeta1.2, and Kvbeta1.2 eliminated the increase of Kv2.1 and Kv4.3 currents produced by KChAP. Both KChAP and Kvbeta1.2 are expressed in cardiomyocytes, where Kv1.5 and Kv2.1 produce sustained outward currents and Kv4.3 and Kv1.4 generate transient outward currents. Because they interact, either KChAP or Kvbeta1.2 may alter both sustained and transient cardiac Kv currents. The interaction of these two different classes of modulatory proteins may constitute a novel mechanism for regulating cardiac K+ currents.
Kuryshev
Y A
YA
The Rammelkamp Center for Education and Research, MetroHealth Campus, Cleveland, Ohio 44109, USA.
Wible
B A
BA
Gudz
T I
TI
Ramirez
A N
AN
Brown
A M
AM
D000818:Animals; D015152:Blotting, Northern; D001923:Brain Chemistry; D019556:COS Cells; D017930:Genes, Reporter; D006801:Humans; D051663:Kv1.2 Potassium Channel; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D050828:Protein Inhibitors of Activated STAT; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014982:Xenopus laevis
C496969:KCNA2 protein, human; C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D018832:Molecular Chaperones; C484745:PIAS3 protein, human; C112253:Pias3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D050828:Protein Inhibitors of Activated STAT; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins