PMID- 10636900
OWN - NLM
STAT- MEDLINE
DCOM- 20000224
LR  - 20191210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 3
DP  - 2000 Jan 21
TI  - Transport and pharmacological properties of nine different human Na, K-ATPase
      isozymes.
PG  - 1976-86
AB  - Na,K-ATPase plays a crucial role in cellular ion homeostasis and is the
      pharmacological receptor for digitalis in man. Nine different human Na,K-ATPase
      isozymes, composed of 3 alpha and beta isoforms, were expressed in Xenopus
      oocytes and were analyzed for their transport and pharmacological properties.
      According to ouabain binding and K(+)-activated pump current measurements, all
      human isozymes are functional but differ in their turnover rates depending on the
      alpha isoform. On the other hand, variations in external K(+) activation are
      determined by a cooperative interaction mechanism between alpha and beta isoforms
      with alpha2-beta2 complexes having the lowest apparent K(+) affinity. alpha
      Isoforms influence the apparent internal Na(+) affinity in the order alpha1 >
      alpha2 > alpha3 and the voltage dependence in the order alpha2 > alpha1 > alpha3.
      All human Na,K-ATPase isozymes have a similar, high affinity for ouabain.
      However, alpha2-beta isozymes exhibit more rapid ouabain association as well as
      dissociation rate constants than alpha1-beta and alpha3-beta isozymes. Finally,
      isoform-specific differences exist in the K(+)/ouabain antagonism which may
      protect alpha1 but not alpha2 or alpha3 from digitalis inhibition at
      physiological K(+) levels. In conclusion, our study reveals several new
      functional characteristics of human Na,K-ATPase isozymes which help to better
      understand their role in ion homeostasis in different tissues and in digitalis
      action and toxicity.
FAU - Crambert, G
AU  - Crambert G
AD  - Institut de Pharmacologie et de Toxicologie de l'Universite, Rue du Bugnon 27,
      CH-1005 Lausanne, Switzerland.
FAU - Hasler, U
AU  - Hasler U
FAU - Beggah, A T
AU  - Beggah AT
FAU - Yu, C
AU  - Yu C
FAU - Modyanov, N N
AU  - Modyanov NN
FAU - Horisberger, J D
AU  - Horisberger JD
FAU - Lelievre, L
AU  - Lelievre L
FAU - Geering, K
AU  - Geering K
LA  - eng
GR  - GM-54997/GM/NIGMS NIH HHS/United States
GR  - HL-36573/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Complementary)
RN  - 5ACL011P69 (Ouabain)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - Biological Transport
MH  - Cell Membrane/enzymology
MH  - Cloning, Molecular
MH  - Dose-Response Relationship, Drug
MH  - Electrophysiology
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - *Isoenzymes
MH  - Kinetics
MH  - Oocytes/metabolism
MH  - Ouabain/antagonists & inhibitors/metabolism
MH  - Potassium/pharmacology
MH  - RNA, Complementary/metabolism
MH  - Sodium/pharmacology
MH  - Sodium-Potassium-Exchanging ATPase/genetics/*metabolism/*pharmacology
MH  - Xenopus/metabolism
EDAT- 2000/01/15 09:00
MHDA- 2000/02/26 09:00
CRDT- 2000/01/15 09:00
PHST- 2000/01/15 09:00 [pubmed]
PHST- 2000/02/26 09:00 [medline]
PHST- 2000/01/15 09:00 [entrez]
AID - 10.1074/jbc.275.3.1976 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 21;275(3):1976-86. doi: 10.1074/jbc.275.3.1976.