Molecular cloning and functional expression of cDNA encoding a second class of inward rectifier potassium channels in the mouse brain.
We have cloned a second class of inward rectifier potassium channels, designated MB-IRK2, from a mouse brain cDNA library. The amino acid sequence of this clone shares 70% identity with the mouse IRK1. Xenopus oocytes injected with cRNA derived from MB-IRK2 expressed a K+ current, which showed inward rectifying channel characteristics similar to the MB-IRK1 current. In contrast to the MB-IRK1 current, however, the MB-IRK2 current exhibited significant inactivation during hyperpolarizing pulses. In patch clamp experiments with 140 mM K+ in the pipette, the single channel conductance of MB-IRK2 was 34.2 +/- 2.1 picosiemens (n = 5), a value significantly larger than that of MB-IRK1 (22.2 +/- 3.0 picosiemens, n = 5). Consistent with the whole cell current, the steady-state open probability (Po) of the MB-IRK2 channel decreased with hyperpolarization, whereas that of the MB-IRK1 remained constant. Northern blot analysis revealed the mRNA for MB-IRK2 to be expressed in forebrain, cerebellum, heart, kidney, and skeletal muscle. In the brain, the abundance of mRNA for MB-IRK2 was much higher in cerebellum than in forebrain and vice versa in the case of MB-IRK1. These results demonstrate that the IRK family is composed of multiple genes, which may play heterogenous functional roles in various organs, including the central nervous system.
Takahashi
N
N
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Morishige
K
K
Jahangir
A
A
Yamada
M
M
Findlay
I
I
Koyama
H
H
Kurachi
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D014981:Xenopus
D018076:DNA, Complementary; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C089327:inward rectifier potassium channel 2