| Summary: | 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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