Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.
Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.
The functional properties of heteromeric
Kir4.1/Kir5.1 channels are profoundly different to their parental subunits; homomeric Kir4.1
channels are only mildly sensitive to intracellular pH (IC50 ∼ 6.0) and have a single channel
conductance of approximately 10 pS. By contrast, heteromeric Kir4.1/Kir5.1 channels are
highly sensitive to intracellular pH (IC50 ∼ 6.8) and have a single channel conductance of
∼45 pS with multiple short-lived, subconductance states (Pessia 1996 , Pessia 2001 , Konstas , Rapedius , Tanemoto , Giwa , Xu ).
Given the tetrameric nature of the K+ channel pore it is assumed that the central ion conduction
pathway is not formed unless all four of the gating helices are in their ‘open’ conformation.
Therefore, one structural model to explain the existence of K+ channel subconductance states
is that these sublevels originate at the helix-bundle crossing due to successive movements of
the four gating helices from the closed to open states, each movement producing a ‘partial’
opening of the channel on the way to the fully open state (Bezanilla ). An alternative model
proposed by Chapman & VanDongen suggests that the sublevels seen in the voltage-gated
Kv2.1 channel originate from asymmetric conformations adopted by the selectivity filter in
response to individual movements of the four gating helices (Chapman 2005 ). Either way, both models
assume that the allosteric interactions between identical subunits in a homomeric channel are
highly cooperative, resulting in rapid transitions between the sublevels which are not resolved
in the timescales of most single-channel recordings, making their analysis difficult, especially
when obscured by noise and filtering. This behaviour, therefore, gives the appearance of a
smooth and binary transition between the open and closed states (Bezanilla , Chapman 2005 ).
basolateral small conductance K+ channel in the distal nephron as well as pH-sensitive K+
channels in chemosensitive neurons (Pessia 1996 , Pessia 2001 ). Likewise, heteromeric Kir4.2/Kir5.1 channels have
been reported in hepatic and pancreatic tissues (Pessia 2001 , Pearson , Hill ).
models of ion channel gating are binary and alternate between two discrete permeation states:
open and closed. The movement between these two states is thought to be controlled by a ‘gate’
which physically impedes the flow of ions in the closed state but which moves out of the way
during the open state. However, such simple models of channel gating are challenged by the
observation of intermediate conductance, or ‘subconductance’ levels, such as those seen in
heteromeric Kir4.0/Kir5.1 channels as well as many other types of ion channel (Bezanilla , Fox , Chapman 2005 , Chapman 1997 ).