PMID- 10097176
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a
      transmembrane beta-subunit homolog.
PG  - 4137-42
AB  - Voltage-dependent and calcium-sensitive K+ (MaxiK) channels are key regulators of
      neuronal excitability, secretion, and vascular tone because of their ability to
      sense transmembrane voltage and intracellular Ca2+. In most tissues, their
      stimulation results in a noninactivating hyperpolarizing K+ current that reduces 
      excitability. In addition to noninactivating MaxiK currents, an inactivating
      MaxiK channel phenotype is found in cells like chromaffin cells and hippocampal
      neurons. The molecular determinants underlying inactivating MaxiK channels remain
      unknown. Herein, we report a transmembrane beta subunit (beta2) that yields
      inactivating MaxiK currents on coexpression with the pore-forming alpha subunit
      of MaxiK channels. Intracellular application of trypsin as well as deletion of 19
      N-terminal amino acids of the beta2 subunit abolished inactivation of the alpha
      subunit. Conversely, fusion of these N-terminal amino acids to the
      noninactivating smooth muscle beta1 subunit leads to an inactivating phenotype of
      MaxiK channels. Furthermore, addition of a synthetic N-terminal peptide of the
      beta2 subunit causes inactivation of the MaxiK channel alpha subunit by occluding
      its K+-conducting pore resembling the inactivation caused by the "ball" peptide
      in voltage-dependent K+ channels. Thus, the inactivating phenotype of MaxiK
      channels in native tissues can result from the association with different beta
      subunits.
FAU - Wallner, M
AU  - Wallner M
AD  - Department of Anesthesiology, University of California, Los Angeles, CA
      90095-1778, USA.
FAU - Meera, P
AU  - Meera P
FAU - Toro, L
AU  - Toro L
LA  - eng
SI  - GENBANK/AF099137
GR  - R01 HL054970/HL/NHLBI NIH HHS/United States
GR  - HL54970/HL/NHLBI NIH HHS/United States
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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (KCNMA1 protein, human)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channel alpha Subunits)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channel beta Subunits)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Calcium-Activated)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/*physiology
MH  - Conserved Sequence
MH  - Databases as Topic
MH  - Expressed Sequence Tags
MH  - Female
MH  - Glycosylation
MH  - Humans
MH  - In Vitro Techniques
MH  - Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
MH  - Large-Conductance Calcium-Activated Potassium Channel beta Subunits
MH  - Large-Conductance Calcium-Activated Potassium Channels
MH  - Macromolecular Substances
MH  - Male
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Neurons/*physiology
MH  - Oocytes/drug effects/physiology
MH  - Organ Specificity
MH  - Potassium Channels/*chemistry/genetics/*physiology
MH  - *Potassium Channels, Calcium-Activated
MH  - Protein Structure, Secondary
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Xenopus laevis
PMC - PMC22433
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1073/pnas.96.7.4137 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4137-42. doi: 10.1073/pnas.96.7.4137.