UC Irvine

Ion channels form transmembrane water-filled pores that allow ions to cross membranes in a rapid and selective fashion. The amino acid residues that line these pores have been sought to reveal the mechanisms of ion conduction and selectivity1,2,3,4,5,6,7. The pore (P) loop8 is a stretch of residues that influences single-channel-current amplitude, selectivity among ions and open-channel blockade2,3,5 and is conserved in potassium-channel subunits previously recognized to contribute to pore formation5,9. To date, potassium-channel pores have been shown to form by symmetrical alignment of four P loops around a central conduction pathway10,11,12. Here we show that the selectivity-determining pore region of the voltage-gated potassium channel of human heart through which the IKs current passes includes the transmembrane segment of the non-P-loop protein minK. Two adjacent residues in this segment of minK are exposed in the pore on either side of a short barrier that restricts the movement of sodium, cadmium and zinc ions across the membrane. Thus, potassium-selective pores are not restricted to P loops or a strict P-loop geometry.