Abstract
Current through the σ-pore was first detected in hKv1.3_V388C channels, where the V388C mutation in hKv1.3 channels opened a new pathway (σ-pore) behind the central α-pore. Typical for this mutant channel was inward current at potentials more negative than -100 mV when the central α-pore was closed. The α-pore blockers such as TEA+ and peptide toxins (CTX, MTX) could not reduce current through the σ-pore of hKv1.3_V388C channels. This new pathway would proceed in parallel to the α-pore in the S6-S6 interface gap. To see whether this phenomenon is restricted to hKv1.3 channels we mutated hKv1.2 at the homologue position (hKv1.2_V370C). By overexpression of hKv1.2_V370C mutant channels in COS-7 cells we could show typical σ-currents. The electrophysiological properties of the σ-pore in hKv1.3_V388C and hKv1.2_V370C mutant channels were similar. The σ-pore of hKv1.2_V370C channels was most permeable to Na+ and Li+ whereas Cl- and protons did not influence current through the σ-pore. Tetraethylammonium (TEA+), charybdotoxin (CTX) and maurotoxin (MTX), known α-pore blockers, could not reduce current through the σ-pore of hKv1.2_V370C channels. Taken together we conclude that the observation of σ-pore currents is not restricted to Kv1.3 potassium channels but can also be observed in a closely related potassium channel. This finding could have implications in the treatment of different ion channel diseases linked to mutations of the respective channels in regions close to homologue position investigated by us.
Highlights
Earlier studies showed that mutation in voltage-gated and potassium channels could open other pathways besides the central α-pore through the complex channel molecules
Observation of σ-pore currents in mutant hKv1.2_V370C potassium channels with 100-ms (B,D,F,H) or 200-ms (A,C,E,G) depolarizing pulses from the holding potential of -120 mV to +40 mV followed by 100-ms hyperpolarizing pulses to -180 mV in [160 Na+ + 4.5 K+]o and in [164.5 K+]o external bath solution
An almost identical current behavior is shown in the bottom row (C,D) of Fig 1, where ramp currents through hKv1.2_wt (C) and hKv1.2_V370C (D) mutant channels are shown in bathing solutions as described for Fig 1A and 1B
Summary
Earlier studies showed that mutation in voltage-gated and potassium channels could open other pathways besides the central α-pore through the complex channel molecules. These pathways could be described as alternative pores and were initially observed with mutations in the voltage-sensing domain (S1-S4) of the channels. Kv1.2 and Kv1.3 channels are voltage-activated channels that open with depolarizations Both channel proteins consist of four subunits. The N- and C-terminal regions of the channels are located at the intracellular side [4]. Each subunit of these channels contain six membrane-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
