Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line.
We have cloned the human homologue of the inward rectifier K+ channel from both heart and brain tissue (HHBIRK1). The human clones were identical to each other in their coding regions and were highly homologous to the mouse macrophage (IRK1) channel. The inward rectifier currents from human and mouse clones were characterized using a novel strategy for stable ion channel expression in a human cell line. The permeability of the expressed inwardly rectifying channels was greater for K+ than for Rb+, whereas no current was observed when K+ was replaced by Na+. A prominent time- and voltage-dependent block was observed in the presence of Ba2+, whereas a small decay in the steady-state current was observed with millimolar concentrations of Na+. Single-channel conductances of 49.1 +/- 3.3 pS (n = 6) and 40.2 +/- 2.5 pS (n = 3) (P = 0.005) were obtained for the HHBIRK1 and IRK1 clones, respectively. These results indicate that sequence dissimilarities between human and mouse inward rectifier K+ channels may have significant functional consequences.
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
M D
MD
Ashen
B
B
O'Rourke
K A
KA
Kluge
D C
DC
Johns
G F
GF
Tomaselli
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003001:Cloning, Molecular; D017931:DNA Primers; D005333:Fetus; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000494:pharmacology; D014162:Transfection
D017931:DNA Primers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D001464:Barium; D012964:Sodium