Proks P , Capener CE , Jones P , Ashcroft FM .

Wellcome Trust

	Scheme S1.
	Scheme S2.
	Scheme S3.
	Figure 1. (A) Single-channel currents recorded at −130 mV from two different inside-out patches excised from an oocyte expressing Kir6.2 and SUR1. Currents were recorded in the presence of 10 mM (above) or 140 mM (below) symmetrical K+ solutions. The dashed line indicates the zero current level.
	Figure 2. (A) Single-channel currents recorded at −60 mV from an inside-out patch excised from an oocyte expressing Kir6.2/SUR1, Kir1.1, or Kir2.1, as indicated. Currents were recorded in a symmetrical 140-mM solution. The dashed line indicates the zero current level. (B) Sequence of the pore loop of Kir6.2 compared with that of some other types of K+ channel. Arrows indicate the mutated residues.
	Figure 3. (A) Single-channel currents (left) and corresponding amplitude histograms (right) recorded at −60 mV from an inside-out patch excised from an oocyte expressing the channel indicated. The dashed line indicates the zero current level. (B) Mean current-voltage relations measured for Kir6.2/SUR1 (O, n = 3), Kir6.2-V127T/SUR1 (▪, n = 3), Kir6.2-G135F/SUR1 (•, n = 3), and Kir6.2-M137C/SUR1 (□, n = 3) channels in symmetrical 140-mM K+. The lines are fitted through the data points using a spline function.
	Figure 4. (A) Open time distributions measured at −60 mV for wild-type (WT) and mutant Kir6.2/SUR1 channels, as indicated. The lines are fitted to either one exponential (WT, G135F) or the sum of two exponentials (V127T and M137C) with the time constants indicated. (B) Closed time distributions measured at −60 mV for wild-type (WT) and mutant Kir6.2/SUR1 channels, as indicated. The lines are fitted to the sum of three exponentials with the time constants indicated.
	Figure 5. (A) Single-channel currents recorded at −60 mV from an inside-out patch excised from oocytes expressing SUR1 and either Kir6.2, Kir6.2-V127T, or Kir6.2-V127T + F133Y. The dashed line indicates the zero current level. (B) Mean current-voltage relations measured for Kir6.2/SUR1 (○, n = 3), Kir6.2-V127T/SUR1 (▪, n = 3), or Kir6.2-V127T+F133Y/SUR1 (•, n = 3). The lines are fitted through the data points using a spline function.
	Figure 6. Mean kinetic parameters for wild-type and mutant channels measured at −60 mV (n = 5). *P < 0.05.
	Figure 7. (A) Molecular model of the structure of the pore of Kir6.2 based on that of KcsA. The positions of the putative fast and slow gates are indicated. (red) M1-helix, (green) P-helix and filter, and (blue) M2-helix. (B) Molecular model of the selectivity filter of Kir6.2 based on that of KcsA. Residues that affect gating when mutated are highlighted ([magenta] V127, [yellow] G135; and [cyan] M137).

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