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Contributions of intracellular ions to kv channel voltage sensor dynamics.

Goodchild SJ, Fedida D - Front Pharmacol (2012)

Bottom Line: However, several other factors not directly linked to the voltage-dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity, and block of the channel by intracellular ligands.There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization, and relaxation processes of the voltage sensor.These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia Vancouver, BC, Canada.

ABSTRACT
Voltage-sensing domains (VSDs) of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K(+) ions to flow. Conformational transitions within the VSD are induced by changes in the applied voltage across the membrane field. However, several other factors not directly linked to the voltage-dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity, and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization, and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

No MeSH data available.


Overview of Kv channel structure. (A) A top down view of the Kv1.2 open state channel tetramer (PDB: 2A79) with the voltage-sensing domains (S1–S4) in color. The charge carrying S4 segment of the voltage sensor domain is highlighted magenta and the pore domain S5–S6 segments are gray. (B) Side view of two pore forming subunits of the Kv1.2 illustrating the selectivity filter containing two K+ ions of a possible four in positions 2 and 4 shown in blue and a K+ ion residing in the intracellular cavity in magenta.
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Figure 1: Overview of Kv channel structure. (A) A top down view of the Kv1.2 open state channel tetramer (PDB: 2A79) with the voltage-sensing domains (S1–S4) in color. The charge carrying S4 segment of the voltage sensor domain is highlighted magenta and the pore domain S5–S6 segments are gray. (B) Side view of two pore forming subunits of the Kv1.2 illustrating the selectivity filter containing two K+ ions of a possible four in positions 2 and 4 shown in blue and a K+ ion residing in the intracellular cavity in magenta.

Mentions: Voltage-gated potassium channels (Kv) sense membrane voltage and underlie the repolarization of electrically excitable cells (Hille, 2001). This task is achieved by the division of the function of the channels into voltage-sensing domain (VSD) and ion conducting pore domain as shown in Figure 1A (Long et al., 2005b). Charged residues in the S4 transmembrane segment of the VSD move in response to changes in the membrane electrical field and this motion is translated through a coupling mechanism involving S4–S5 linker contacts with the bottom of S6-lined pore domain to open or close the intracellular gate of ionic conductance (Lee et al., 2009). The tight coupling between the two domains allows movements in one domain to be translated rapidly into movements in the other thus creating highly sensitive voltage-gated channels.


Contributions of intracellular ions to kv channel voltage sensor dynamics.

Goodchild SJ, Fedida D - Front Pharmacol (2012)

Overview of Kv channel structure. (A) A top down view of the Kv1.2 open state channel tetramer (PDB: 2A79) with the voltage-sensing domains (S1–S4) in color. The charge carrying S4 segment of the voltage sensor domain is highlighted magenta and the pore domain S5–S6 segments are gray. (B) Side view of two pore forming subunits of the Kv1.2 illustrating the selectivity filter containing two K+ ions of a possible four in positions 2 and 4 shown in blue and a K+ ion residing in the intracellular cavity in magenta.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376422&req=5

Figure 1: Overview of Kv channel structure. (A) A top down view of the Kv1.2 open state channel tetramer (PDB: 2A79) with the voltage-sensing domains (S1–S4) in color. The charge carrying S4 segment of the voltage sensor domain is highlighted magenta and the pore domain S5–S6 segments are gray. (B) Side view of two pore forming subunits of the Kv1.2 illustrating the selectivity filter containing two K+ ions of a possible four in positions 2 and 4 shown in blue and a K+ ion residing in the intracellular cavity in magenta.
Mentions: Voltage-gated potassium channels (Kv) sense membrane voltage and underlie the repolarization of electrically excitable cells (Hille, 2001). This task is achieved by the division of the function of the channels into voltage-sensing domain (VSD) and ion conducting pore domain as shown in Figure 1A (Long et al., 2005b). Charged residues in the S4 transmembrane segment of the VSD move in response to changes in the membrane electrical field and this motion is translated through a coupling mechanism involving S4–S5 linker contacts with the bottom of S6-lined pore domain to open or close the intracellular gate of ionic conductance (Lee et al., 2009). The tight coupling between the two domains allows movements in one domain to be translated rapidly into movements in the other thus creating highly sensitive voltage-gated channels.

Bottom Line: However, several other factors not directly linked to the voltage-dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity, and block of the channel by intracellular ligands.There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization, and relaxation processes of the voltage sensor.These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia Vancouver, BC, Canada.

ABSTRACT
Voltage-sensing domains (VSDs) of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K(+) ions to flow. Conformational transitions within the VSD are induced by changes in the applied voltage across the membrane field. However, several other factors not directly linked to the voltage-dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity, and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization, and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

No MeSH data available.