PMID- 9450939
OWN - NLM
STAT- MEDLINE
DCOM- 19980305
LR  - 20190508
IS  - 0022-1295 (Print)
IS  - 1540-7748 (Electronic)
IS  - 0022-1295 (Linking)
VI  - 111
IP  - 2
DP  - 1998 Feb
TI  - The interaction of Na+ and K+ in voltage-gated potassium channels. Evidence for 
      cation binding sites of different affinity.
PG  - 195-206
AB  - Voltage-gated potassium (K+) channels are multi-ion pores. Recent studies suggest 
      that, similar to calcium channels, competition between ionic species for 
      intrapore binding sites may contribute to ionic selectivity in at least some K+ 
      channels. Molecular studies suggest that a putative constricted region of the 
      pore, which is presumably the site of selectivity, may be as short as one ionic 
      diameter in length. Taken together, these results suggest that selectivity may 
      occur at just a single binding site in the pore. We are studying a chimeric K+ 
      channel that is highly selective for K+ over Na+ in physiological solutions, but 
      conducts Na+ in the absence of K+. Na+ and K+ currents both display slow (C-type) 
      inactivation, but had markedly different inactivation and deactivation kinetics; 
      Na+ currents inactivated more rapidly and deactivated more slowly than K+ 
      currents. Currents carried by 160 mM Na+ were inhibited by external K+ with an 
      apparent IC50 <30 microM. K+ also altered both inactivation and deactivation 
      kinetics of Na+ currents at these low concentrations. In the complementary 
      experiment, currents carried by 3 mM K+ were inhibited by external Na+, with an 
      apparent IC50 of approximately 100 mM. In contrast to the effects of low [K+] on 
      Na+ current kinetics, Na+ did not affect K+ current kinetics, even at 
      concentrations that inhibited K+ currents by 40-50%. These data suggest that Na+ 
      block of K+ currents did not involve displacement of K+ from the high affinity 
      site involved in gating kinetics. We present a model that describes the 
      permeation pathway as a single high affinity, cation-selective binding site, 
      flanked by low affinity, nonselective sites. This model quantitatively predicts 
      the anomalous mole fraction behavior observed in two different K+ channels, 
      differential K+ and Na+ conductance, and the concentration dependence of K+ block 
      of Na+ currents and Na+ block of K+ currents. Based on our results, we 
      hypothesize that the permeation pathway contains a single high affinity binding 
      site, where selectivity and ionic modulation of gating occur.
FAU - Kiss, L
AU  - Kiss L
AD  - Department of Physiology and Neurobiology, University of Connecticut, Storrs, 
      Connecticut 06269, USA.
FAU - Immke, D
AU  - Immke D
FAU - LoTurco, J
AU  - LoTurco J
FAU - Korn, S J
AU  - Korn SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Gen Physiol
JT  - The Journal of general physiology
JID - 2985110R
RN  - 0 (Cations)
RN  - 0 (Potassium Channels)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9NEZ333N27 (Sodium)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Binding Sites/genetics/physiology
MH  - Cations/metabolism
MH  - Cell Membrane Permeability/physiology
MH  - Cells, Cultured
MH  - Electrophysiology
MH  - Humans
MH  - Ion Channel Gating/genetics/physiology
MH  - Liver/metabolism
MH  - Patch-Clamp Techniques
MH  - Potassium/*physiology
MH  - Potassium Channels/drug effects/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Sodium/*physiology
PMC - PMC2222767
EDAT- 1998/03/07 00:00
MHDA- 1998/03/07 00:01
PMCR- 1998/08/01
CRDT- 1998/03/07 00:00
PHST- 1998/03/07 00:00 [pubmed]
PHST- 1998/03/07 00:01 [medline]
PHST- 1998/03/07 00:00 [entrez]
PHST- 1998/08/01 00:00 [pmc-release]
AID - 10.1085/jgp.111.2.195 [doi]
PST - ppublish
SO  - J Gen Physiol. 1998 Feb;111(2):195-206. doi: 10.1085/jgp.111.2.195.