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Figure 3. Long pore plugging model of inward rectification. (A) Reaction scheme for the “long pore” model of direct open channel block by spermine (S) proposed by Lopatin et al. (1995) (shaded area), modified to include direct competitive block by philanthotoxin (T). Cartoons illustrate states in which the channel pore is open (O), blocked by spermine (B1–B3), philanthotoxin (B4), or both spermine and philanthotoxin (B5). K1–5 represent equilibrium constants (kreverse/kforward) for the various transitions. See text for details. (B–C) Fits of the direct block model in A to the experimental data for the spermine–philanthotoxin interaction in wild-type Kir2.1 shown in Fig. 3 B, where ○ are spermine alone, • are spermine + philanthotoxin, and gray crosses are normalized spermine + philanthotoxin. Model parameters in B: K1 = 7.75 × 10−5 M, K2 = 7.75 × 10−5 M, K3 = 7.75 × 10−5 M, K4 = 47 × 10−9 M, K5 = 47 × 10−9 M. In C, the B5 state was disabled by increasing K5 to 103 M. In neither case could the model reproduce quantitatively the increase in K0.5 for spermine in the presence of philanthotoxin.

Image published in: John SA and Weiss JN (1999)

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