Cloning and characterization of Kir3.1 (GIRK1) C-terminal alternative splice variants.
Southern blot analysis of RT-PCR products from brain and heart revealed multiple products for a C-terminal region of Kir3.1. Sequencing yielded clones for wild-type Kir3.1 and three Kir3.1 C-terminal alternative splice variants, including a unique alternative exon. Two of these variants encoded truncated Kir3.1 molecules. Tissue distribution and electrophysiological characterization of a single truncated variant, Kir3.1(00) were then examined. Kir3.1 channels are gated by G-protein beta gamma-subunits binding to the C-terminal domain, thus, the truncation of Kir3.1(00) removes a major functional domain. When incorporated into heteromeric channels with other family members (Kir3.1, 3.2 or 3.4) several functional changes were observed: (1) Kir3.1(00) changes G-protein activation of Kir3 channels; (2) Kir3.1(00) is restricted in its ability to assemble with other channel subunits as heteromers; and (3) incorporation of Kir3.1(00) into heteromeric channel complexes alters the kinetics of channel re-activation.
Nelson
C S
CS
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201, USA. nelsonc@ohsu.edu
Marino
J L
JL
Allen
C N
CN
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D003001:Cloning, Molecular; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D014158:Transcription, Genetic; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497068:Kcnj3 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying