科研之友
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摘要
Voltage-gated potassium channels are proteins composed of four subunits consisting of six membrane-spanning segments S1-S6, with S4 as the voltage sensor. The region between S5 and S6 forms the potassium-selective ion-conducting central alpha-pore. Recent studies showed that mutations in the voltage sensor of the Shaker channel could disclose another ion permeation pathway through the voltage-sensing domain (S1-S4) of the channel, the alpha-pore. In our studies we used the voltage-gated hKv1.3 channel, and the insertion of a cysteine at position V388C (Shaker position 438) generated a current through the alpha-pore in high potassium outside and an inward current at hyperpolarizing potentials carried by different cations like Na(+), Li(+), Cs(+), and NH(4)(+). The observed inward current looked similar to the omega-current described for the R1C/S Shaker mutant channel and was not affected by some pore blockers like charybdotoxin and tetraethylammonium but was inhibited by a phenylalkylamine blocker (verapamil) that acts from the intracellular side. Therefore, we hypothesize that the hKv1.3_V388C mutation in the P-region generated a channel with two ion-conducting pathways. One, the alpha-pore allowing K(+) flux in the presence of K(+), and the second pathway, the sigma-pore, functionally similar but physically distinct from the omega-pathway. The entry of this new pathway (alpha-pore) is presumably located at the backside of Y395 (Shaker position 445), proceeds parallel to the alpha-pore in the S6-S6 interface gap, ending between S5 and S6 at the intracellular side of one alpha-subunit, and is blocked by verapamil.
- 出版日期2011-6-3
