Year-end Sale % OFF 
Abstract
Voltage-gated potassium channels are transmembrane proteins made up of four subunits, each comprising six transmembrane (S1-S6) segments. S1-S4 form the voltage-sensing domain and S5-S6 the pore domain with its central pore. The sensor domain detects membrane depolarization and transmits the signal to the activation gates situated in the pore domain, thereby leading to channel opening. An understanding of the mechanism by which the sensor communicates the signal to the pore requires knowledge of the structure of the interface between the voltage-sensing and pore domains. Toward this end, we have introduced single cysteine mutations into the extracellular end of S4 (positions 356 and 357) in conjunction with a cysteine in S5 (position 418) of the Shaker channel and expressed the mutants in Xenopus oocytes. We then examined the propensity of each pair of engineered cysteines to form a metal bridge or a disulfide bridge, respectively, by examining the effect of Cd2+ ions and copper phenanthroline on the K+ conductance of a whole oocyte. Both reagents reduced currents through the S357C,E418C double mutant channel, presumably by restricting the movements necessary for coupling the voltage-sensing function to pore opening. This inhibitory effect was seen in the closed state of the channel and with heteromers composed of S357C and E418C single mutant subunits; no effect was seen with homomers of any of the single mutant channels. These data indicate that the extracellular end of S4 lies in close proximity to the extracellular end of the S5 of the neighboring subunit in closed channels.
Highlights
The inactivation gate, which confers C-type inactivation in Kv channels, appears to be located at the extracellular end of the pore above the selectivity filter [6, 12, 13]
The x-ray structure is not known for any member of the Kv channel family, current evidence suggests that the pore domain of the channel is homologous to bacterial potassium channels [7,8,9]
We have investigated the possibility that the voltage-sensing S4 segment lies in close proximity to the perimeter of the pore domain at the extracellular end of the Shaker potassium channel
Summary
The inactivation gate, which confers C-type inactivation in Kv channels, appears to be located at the extracellular end of the pore above the selectivity filter [6, 12, 13]. The pore and the voltage-sensing domains are functionally coupled such that when the membrane is depolarized the subsequent movement of the voltage-sensing domains leads to channel opening [1,2,3,4,5]. Some channel pores contain inactivation gates that close during depolarization, resulting in the This is accompanied by the entry of several of the cytoplasmically accessible S4 residues into the membrane bilayer [16, 17]. The movements of S4 and the gates are known to some extent, the mechanism whereby the movements in the voltage sensor are coupled to the motion of pore gates is not termination of ion flux, the activation gates may known. Structure perturbation studies have revealed residues remain open [2, 3, 6]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
