Limits...
Pore size matters for potassium channel conductance

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance.

No MeSH data available.


Related in: MedlinePlus

K+ channel structural topology. Surface representation of Kv (Kv1.2/2.1 chimera; left) and BK (Slo2.2; right) structures. Green and yellow colors represent the voltage-sensing domain (VSD) and the pore domain (PD), respectively. The green arrows show the putative conduction paths for ions that in Kv channels K+ access/exit through the lateral windows of the “hanging” T1 domain (the gondola in cyan), whereas in BK the ions cross the entire gating ring formed by the RCK domains (in cyan). The pink spheres are K+ ions, and the horizontal discontinued lines indicate the approximate inner and outer boundaries of the membrane. External side is up. The Kv figure is a 6-Å slab prepared with VMD, with −6 < x < 0 (Humphrey et al., 1996). BK front and rear subunits are removed for clarity (inspired by Hite et al. [2015]).
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC5037345&req=5

fig3: K+ channel structural topology. Surface representation of Kv (Kv1.2/2.1 chimera; left) and BK (Slo2.2; right) structures. Green and yellow colors represent the voltage-sensing domain (VSD) and the pore domain (PD), respectively. The green arrows show the putative conduction paths for ions that in Kv channels K+ access/exit through the lateral windows of the “hanging” T1 domain (the gondola in cyan), whereas in BK the ions cross the entire gating ring formed by the RCK domains (in cyan). The pink spheres are K+ ions, and the horizontal discontinued lines indicate the approximate inner and outer boundaries of the membrane. External side is up. The Kv figure is a 6-Å slab prepared with VMD, with −6 < x < 0 (Humphrey et al., 1996). BK front and rear subunits are removed for clarity (inspired by Hite et al. [2015]).

Mentions: There is one more problem with the estimation of the internal pore dimension based on the radius of capture for BK and Kv channels. These measurements disregard the contribution of important intracellular domains in both proteins, leading to an oversimplified structural image (Long et al., 2005a; Hite et al., 2015). Both BK and Kv channels have tetramerization domains near the internal entrance (Kobertz and Miller, 1999; Krishnamoorthy et al., 2005; Hite et al., 2015). In Kv channels, the four tetramerization domains (T1) form a structure known as “the hanging gondola” because it hangs from the pore domain through four linkers, leaving four side-facing openings for ion transport (Fig. 3; Kobertz and Miller, 1999; Long et al., 2007). Meanwhile, the structure of Slo2.2, a BK channel, shows the calcium-dependent gating ring forming a funnel structure that could guide ions into the pore cavity (Hite et al., 2015). Both structures project negative electrostatic potential into the permeation pathway, raising local K+ concentration, but contribute, at most, to 30% to the unitary current (Kobertz and Miller, 1999; Budelli et al., 2013; Hite et al., 2015).


Pore size matters for potassium channel conductance
K+ channel structural topology. Surface representation of Kv (Kv1.2/2.1 chimera; left) and BK (Slo2.2; right) structures. Green and yellow colors represent the voltage-sensing domain (VSD) and the pore domain (PD), respectively. The green arrows show the putative conduction paths for ions that in Kv channels K+ access/exit through the lateral windows of the “hanging” T1 domain (the gondola in cyan), whereas in BK the ions cross the entire gating ring formed by the RCK domains (in cyan). The pink spheres are K+ ions, and the horizontal discontinued lines indicate the approximate inner and outer boundaries of the membrane. External side is up. The Kv figure is a 6-Å slab prepared with VMD, with −6 < x < 0 (Humphrey et al., 1996). BK front and rear subunits are removed for clarity (inspired by Hite et al. [2015]).
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5037345&req=5

fig3: K+ channel structural topology. Surface representation of Kv (Kv1.2/2.1 chimera; left) and BK (Slo2.2; right) structures. Green and yellow colors represent the voltage-sensing domain (VSD) and the pore domain (PD), respectively. The green arrows show the putative conduction paths for ions that in Kv channels K+ access/exit through the lateral windows of the “hanging” T1 domain (the gondola in cyan), whereas in BK the ions cross the entire gating ring formed by the RCK domains (in cyan). The pink spheres are K+ ions, and the horizontal discontinued lines indicate the approximate inner and outer boundaries of the membrane. External side is up. The Kv figure is a 6-Å slab prepared with VMD, with −6 < x < 0 (Humphrey et al., 1996). BK front and rear subunits are removed for clarity (inspired by Hite et al. [2015]).
Mentions: There is one more problem with the estimation of the internal pore dimension based on the radius of capture for BK and Kv channels. These measurements disregard the contribution of important intracellular domains in both proteins, leading to an oversimplified structural image (Long et al., 2005a; Hite et al., 2015). Both BK and Kv channels have tetramerization domains near the internal entrance (Kobertz and Miller, 1999; Krishnamoorthy et al., 2005; Hite et al., 2015). In Kv channels, the four tetramerization domains (T1) form a structure known as “the hanging gondola” because it hangs from the pore domain through four linkers, leaving four side-facing openings for ion transport (Fig. 3; Kobertz and Miller, 1999; Long et al., 2007). Meanwhile, the structure of Slo2.2, a BK channel, shows the calcium-dependent gating ring forming a funnel structure that could guide ions into the pore cavity (Hite et al., 2015). Both structures project negative electrostatic potential into the permeation pathway, raising local K+ concentration, but contribute, at most, to 30% to the unitary current (Kobertz and Miller, 1999; Budelli et al., 2013; Hite et al., 2015).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance.

No MeSH data available.


Related in: MedlinePlus