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Modelling of voltage-dependent gating and sodium currents in the Kv1.5 potassium channel Hesketh, John Christian
Abstract
Activation gating in voltage-gated potassium channels involves multiple closed-closed transitions prior to channel opening. We have examined various voltage-dependent properties of activation gating in the human Kvl.5 potassium channel heterologously expressed in HEK-293 cells. Two gating charge systems have been described in another voltage-gated potassium channel, Shaker, and the analogous charge systems in Kvl.5 share similar features with Shaker. These two charge systems, Ql and Q2, had characteristic voltage-dependence and sensitivity with Wi values of-29.6 ± 1.6 mV, and -2.19 ± 2.09 mV, and effective valences of 1.87 ±0.15 and 5.53 ± 0.27 (e⁻) respectively. The contribution to total gating charge was 0.20 ± 0.04 for Q l , and 0.80 ±0.04 (n=5) for Q2. Using the drug 4-AP to isolate early gating transitons, Ql and Q2 were found to move in a sequential manner during activation. Gating currents resulting from the movement of these two charge systems were modelled with a simple linear sequential scheme and activation gating was considered with respect to gating in other voltage-gated potassium channels and compared with other kinetic models of channel activation. A concerted opening transition was added to this gating current model and the model was used to simulate sodium ionic currents through Kvl.5 channels. C-type inactivated Kvl.5 channels were found to conduct small Na+ ionic currents, while remaining K ⁺ impermeant. Experimental observations and modelling of this ionic current revealed a high Na+ conducting state during recovery from inactivation and a role for external NA ⁺ in the modulation of fast recovery from inactivation was uncovered.
Item Metadata
Title |
Modelling of voltage-dependent gating and sodium currents in the Kv1.5 potassium channel
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2001
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Description |
Activation gating in voltage-gated potassium channels involves multiple closed-closed
transitions prior to channel opening. We have examined various voltage-dependent properties of
activation gating in the human Kvl.5 potassium channel heterologously expressed in HEK-293
cells. Two gating charge systems have been described in another voltage-gated potassium
channel, Shaker, and the analogous charge systems in Kvl.5 share similar features with Shaker.
These two charge systems, Ql and Q2, had characteristic voltage-dependence and sensitivity
with Wi values of-29.6 ± 1.6 mV, and -2.19 ± 2.09 mV, and effective valences of 1.87 ±0.15
and 5.53 ± 0.27 (e⁻) respectively. The contribution to total gating charge was 0.20 ± 0.04 for Q l ,
and 0.80 ±0.04 (n=5) for Q2. Using the drug 4-AP to isolate early gating transitons, Ql and Q2
were found to move in a sequential manner during activation. Gating currents resulting from the
movement of these two charge systems were modelled with a simple linear sequential scheme
and activation gating was considered with respect to gating in other voltage-gated potassium
channels and compared with other kinetic models of channel activation. A concerted opening
transition was added to this gating current model and the model was used to simulate sodium
ionic currents through Kvl.5 channels. C-type inactivated Kvl.5 channels were found to
conduct small Na+ ionic currents, while remaining K ⁺ impermeant. Experimental observations
and modelling of this ionic current revealed a high Na+ conducting state during recovery from
inactivation and a role for external NA ⁺ in the modulation of fast recovery from inactivation was
uncovered.
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Extent |
7672117 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-07-27
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0099523
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2001-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.