PMID- 10228180
OWN - NLM
STAT- MEDLINE
DCOM- 19990622
LR  - 20190508
IS  - 0022-1295 (Print)
IS  - 0022-1295 (Linking)
VI  - 113
IP  - 5
DP  - 1999 May
TI  - Inactivation gating of Kv4 potassium channels: molecular interactions involving
      the inner vestibule of the pore.
PG  - 641-60
AB  - Kv4 channels represent the main class of brain A-type K+ channels that operate in
      the subthreshold range of membrane potentials (Serodio, P., E. Vega-Saenz de
      Miera, and B. Rudy. 1996. J. Neurophysiol. 75:2174- 2179), and their function
      depends critically on inactivation gating. A previous study suggested that the
      cytoplasmic NH2- and COOH-terminal domains of Kv4.1 channels act in concert to
      determine the fast phase of the complex time course of macroscopic inactivation
      (Jerng, H.H., and M. Covarrubias. 1997. Biophys. J. 72:163-174). To investigate
      the structural basis of slow inactivation gating of these channels, we examined
      internal residues that may affect the mutually exclusive relationship between
      inactivation and closed-state blockade by 4-aminopyridine (4-AP) (Campbell, D.L.,
      Y. Qu, R.L. Rasmussen, and H.C. Strauss. 1993. J. Gen. Physiol. 101:603-626;
      Shieh, C.-C., and G.E. Kirsch. 1994. Biophys. J. 67:2316-2325). A double mutation
      V[404,406]I in the distal section of the S6 region of the protein drastically
      slowed channel inactivation and deactivation, and significantly reduced the
      blockade by 4-AP. In addition, recovery from inactivation was slightly faster,
      but the pore properties were not significantly affected. Consistent with a more
      stable open state and disrupted closed state inactivation, V[404,406]I also
      caused hyperpolarizing and depolarizing shifts of the peak conductance-voltage
      curve ( approximately 5 mV) and the prepulse inactivation curve (>10 mV),
      respectively. By contrast, the analogous mutations (V[556,558]I) in a K+ channel 
      that undergoes N- and C-type inactivation (Kv1.4) did not affect macroscopic
      inactivation but dramatically slowed deactivation and recovery from inactivation,
      and eliminated open-channel blockade by 4-AP. Mutation of a Kv4-specific residue 
      in the S4-S5 loop (C322S) of Kv4.1 also altered gating and 4-AP sensitivity in a 
      manner that closely resembles the effects of V[404, 406]I. However, this mutant
      did not exhibit disrupted closed state inactivation. A kinetic model that assumes
      coupling between channel closing and inactivation at depolarized membrane
      potentials accounts for the results. We propose that components of the pore's
      internal vestibule control both closing and inactivation in Kv4 K+ channels.
FAU - Jerng, H H
AU  - Jerng HH
AD  - Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College,
      Philadelphia, Pennsylvania 19107, USA.
FAU - Shahidullah, M
AU  - Shahidullah M
FAU - Covarrubias, M
AU  - Covarrubias M
LA  - eng
GR  - R01 NS032337/NS/NINDS NIH HHS/United States
GR  - T32 AA007463/AA/NIAAA NIH HHS/United States
GR  - AA07463/AA/NIAAA NIH HHS/United States
GR  - NS32337/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Gen Physiol
JT  - The Journal of general physiology
JID - 2985110R
RN  - 0 (KCND1 protein, human)
RN  - 0 (Kcnd1 protein, mouse)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Shal Potassium Channels)
RN  - BH3B64OKL9 (4-Aminopyridine)
SB  - IM
MH  - 4-Aminopyridine/pharmacology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Computer Simulation
MH  - Electrophysiology
MH  - Humans
MH  - Ion Channel Gating/drug effects/genetics/*physiology
MH  - Kinetics
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oocytes/metabolism
MH  - Patch-Clamp Techniques
MH  - Point Mutation/physiology
MH  - Potassium Channels/drug effects/genetics/*physiology
MH  - *Potassium Channels, Voltage-Gated
MH  - Protein Conformation
MH  - Shal Potassium Channels
MH  - Xenopus
PMC - PMC2222907
EDAT- 1999/05/06 00:00
MHDA- 1999/05/06 00:01
CRDT- 1999/05/06 00:00
PHST- 1999/05/06 00:00 [pubmed]
PHST- 1999/05/06 00:01 [medline]
PHST- 1999/05/06 00:00 [entrez]
AID - 10.1085/jgp.113.5.641 [doi]
PST - ppublish
SO  - J Gen Physiol. 1999 May;113(5):641-60. doi: 10.1085/jgp.113.5.641.