The modulatory effect of KNCE1 beta subunits on KCNQ1 K+ channels is transient

University of Bristol (2005) J Physiol 567P, PC154

Poster Communications: The modulatory effect of KNCE1 beta subunits on KCNQ1 K+ channels is transient

Poulsen, Asser Nyander; Kofod, Rasmus; Klaerke, Dan A;

1. Department of Animal- and Veterinary Basic Sciences, The Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, Denmark.

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The one-transmembrane-segment beta-subunit KCNE1 (formerly known as MinK) is known to modulate the characteristics of the voltage-regulated K+ channels of the KCNQ1 type, which are present in various tissues and serves to maintain membrane potential, shape action potentials and transport K+ ions. In heart muscle the combination of KCNE1 and KCNQ1 is essential for proper repolarization during an action potential. It has been hypothesized that KCNE1 forms a protein complex with KCNQ1 in the cell membrane and that the proteins are assembled during synthesis when expressed simultaneously. However, it was recently shown that delayed expression of KCNE1 is still capable of modulating already expressed KCNQ1 channels, suggesting that the coupling of KCNE1 to KCNQ1 can happen in the plasma membrane [1]. KCNE1 and KCNQ1 may have different lifetimes and we therefore asked whether the ion channel characteristics of KCNQ1 channels might change over time after co-expression of KCNQ1 and KCNE1 in Xenopus oocytes as a result of altered relative protein concentrations. A 1:1 mixture of KCNE1 and KCNQ1 mRNA was injected into Xenopus Laevis oocytes and the maximal KCNQ1 mediated current, voltage dependence and channel activation kinetics was measured daily during the following 14 days. During the first 2-3 days the oocytes expressed a typical KCNE1+KCNQ1 current, but subsequently the current characteristics gradually changed and finally after approx. 9 days the current was not significantly different from pure KCNQ1 currents. The observed change in current characteristics did not seem to be caused by alterations in oocyte condition or interference with endogenous components, as the characteristics of KCNQ1 channels expressed alone changed only very little over time. In conclusion our experiments suggest that the KCNE beta-subunit over time may be released from the KCNQ1-KCNE complex. This result favors the hypothesis that KCNE subunits act as modulatory molecules, which may be acutely up and down regulated to modulate ion channels already present in the cell membrane.



Where applicable, experiments conform with Society ethical requirements.

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