PMID- 10026195
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - Calmodulin mediates calcium-dependent activation of the intermediate conductance 
      KCa channel, IKCa1.
PG  - 5746-54
AB  - Small and intermediate conductance Ca2+-activated K+ channels play a crucial role
      in hyperpolarizing the membrane potential of excitable and nonexcitable cells.
      These channels are exquisitely sensitive to cytoplasmic Ca2+, yet their
      protein-coding regions do not contain consensus Ca2+-binding motifs. We
      investigated the involvement of an accessory protein in the Ca2+-dependent gating
      of hIKCa1, a human intermediate conductance channel expressed in peripheral
      tissues. Cal- modulin was found to interact strongly with the cytoplasmic
      carboxyl (C)-tail of hIKCa1 in a yeast two-hybrid system. Deletion analyses
      defined a requirement for the first 62 amino acids of the C-tail, and the binding
      of calmodulin to this region did not require Ca2+. The C-tail of hSKCa3, a human 
      neuronal small conductance channel, also bound calmodulin, whereas that of a
      voltage-gated K+ channel, mKv1.3, did not. Calmodulin co-precipitated with the
      channel in cell lines transfected with hIKCa1, but not with mKv1. 3-transfected
      lines. A mutant calmodulin, defective in Ca2+ sensing but retaining binding to
      the channel, dramatically reduced current amplitudes when co-expressed with
      hIKCa1 in mammalian cells. Co-expression with varying amounts of wild-type and
      mutant calmodulin resulted in a dominant-negative suppression of current,
      consistent with four calmodulin molecules being associated with the channel.
      Taken together, our results suggest that Ca2+-calmodulin-induced conformational
      changes in all four subunits are necessary for the channel to open.
FAU - Fanger, C M
AU  - Fanger CM
AD  - Department of Physiology and Biophysics, University of California, Irvine,
      California 92697, USA.
FAU - Ghanshani, S
AU  - Ghanshani S
FAU - Logsdon, N J
AU  - Logsdon NJ
FAU - Rauer, H
AU  - Rauer H
FAU - Kalman, K
AU  - Kalman K
FAU - Zhou, J
AU  - Zhou J
FAU - Beckingham, K
AU  - Beckingham K
FAU - Chandy, K G
AU  - Chandy KG
FAU - Cahalan, M D
AU  - Cahalan MD
FAU - Aiyar, J
AU  - Aiyar J
LA  - eng
GR  - GM41514/GM/NIGMS NIH HHS/United States
GR  - GMOD54872/GM/NIGMS NIH HHS/United States
GR  - NS14609/NS/NINDS NIH HHS/United States
GR  - etc.
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 (Calcium Channels)
RN  - 0 (Calmodulin)
RN  - 0 (Intermediate-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (KCNN4 protein, human)
RN  - 0 (Kcnn4 protein, rat)
RN  - 0 (Potassium Channels)
RN  - SY7Q814VUP (Calcium)
SB  - IM
SB  - S
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium Channels/chemistry/*metabolism
MH  - Calmodulin/antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Intermediate-Conductance Calcium-Activated Potassium Channels
MH  - *Ion Channel Gating
MH  - Molecular Sequence Data
MH  - *Potassium Channels
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Tumor Cells, Cultured
OTO - NASA
OT  - Non-programmatic
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1074/jbc.274.9.5746 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5746-54. doi: 10.1074/jbc.274.9.5746.