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C-Terminal Tails of Sulfonylurea Receptors Control ADP-Induced Activation and Diazoxide Modulation of ATP-Sensitive K+ Channels by Tetsuro Matsuoka, Kenji.

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Presentation on theme: "C-Terminal Tails of Sulfonylurea Receptors Control ADP-Induced Activation and Diazoxide Modulation of ATP-Sensitive K+ Channels by Tetsuro Matsuoka, Kenji."— Presentation transcript:

1 C-Terminal Tails of Sulfonylurea Receptors Control ADP-Induced Activation and Diazoxide Modulation of ATP-Sensitive K+ Channels by Tetsuro Matsuoka, Kenji Matsushita, Yusuke Katayama, Akikazu Fujita, Kiyoshi Inageda, Masayuki Tanemoto, Atsushi Inanobe, Shizuya Yamashita, Yuji Matsuzawa, and Yoshihisa Kurachi Circulation Research Volume 87(10): November 10, 2000 Copyright © American Heart Association, Inc. All rights reserved.

2 Figure 1. Effects of intracellular ADP, diazoxide, and pinacidil on SUR2A/Kir6.2 (A), SUR2B/Kir6.2 (B), and SUR2-1/Kir6.2 (C) channels. Figure 1. Effects of intracellular ADP, diazoxide, and pinacidil on SUR2A/Kir6.2 (A), SUR2B/Kir6.2 (B), and SUR2-1/Kir6.2 (C) channels. Left, Effects of ADP and diazoxide (DZX) or pinacidil (PIN) on SUR2A/Kir6.2, SUR2B/Kir6.2, and SUR2-1/Kir6.2 channels. ATP, ADP, diazoxide and pinacidil were added to the bath solution as indicated by bars. Middle, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (○) and presence of diazoxide (◍, 30 μmol/L and •, 300 μmol/L). Right, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (○) and presence of pinacidil (□, 1 μmol/L; ▦, 10 μmol/L; and ▪, 100 μmol/L). Relative NPo is expressed as mean±SE. Tetsuro Matsuoka et al. Circ Res. 2000;87: Copyright © American Heart Association, Inc. All rights reserved.

3 Figure 2. Effects of intracellular ADP, diazoxide on SUR1/Kir6
Figure 2. Effects of intracellular ADP, diazoxide on SUR1/Kir6.2 (A), SUR1-2A/Kir6.2 (B), and SUR1-2B/Kir6.2 (C) channels. Figure 2. Effects of intracellular ADP, diazoxide on SUR1/Kir6.2 (A), SUR1-2A/Kir6.2 (B), and SUR1-2B/Kir6.2 (C) channels. Left, Effects of ADP and diazoxide (DZX) on SUR1/Kir6.2, SUR1-2A/Kir6.2, and SUR1-2B/Kir6.2 channels. ATP, ADP and diazoxide were added to the bath solution as indicated by bars. Right, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (○) and presence of diazoxide (◍, 30 μmol/L and •, 300 μmol/L). Relative NPo is expressed as mean±SE. Tetsuro Matsuoka et al. Circ Res. 2000;87: Copyright © American Heart Association, Inc. All rights reserved.

4 Figure 3. Effects of intracellular ADP, diazoxide, and pinacidil on SUR2B(K1348M)/Kir6.2 (A) and SUR1(K1384A)/Kir6.2 (B) channels. Figure 3. Effects of intracellular ADP, diazoxide, and pinacidil on SUR2B(K1348M)/Kir6.2 (A) and SUR1(K1384A)/Kir6.2 (B) channels. Left, Effects of ADP and diazoxide (DZX) or pinacidil (PIN) on SUR2(K1348M)/Kir6.2 and SUR1(K1384A)/Kir6.2 channels. ATP, ADP, and diazoxide were added to the bath solution as indicated by bars. Right, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (○) and presence of diazoxide (◍, 30 μmol/L and •, 300 μmol/L) or pinacidil (□, 100 μmol/L). Relative NPo is expressed as mean±SE. Tetsuro Matsuoka et al. Circ Res. 2000;87: Copyright © American Heart Association, Inc. All rights reserved.

5 Figure 4. ADP and KCO-related domains and possible interaction between NBD2 and C-terminal tail of SURs. The activation of KATP channels by pinacidil, P1075, and levocromakalin requires the TMD and the CL13-14 of SUR2.27 SUR1-segment of TM6-11 and NBD1 are necessary for the ADP-independent action by diazoxide.28 NBD2 is possibly involved in the ADP-dependent activation by diazoxide, and the SUR2A-type C-terminal tail (C42) inhibits it. Figure 4. ADP and KCO-related domains and possible interaction between NBD2 and C-terminal tail of SURs. The activation of KATP channels by pinacidil, P1075, and levocromakalin requires the TMD and the CL13-14 of SUR2.27 SUR1-segment of TM6-11 and NBD1 are necessary for the ADP-independent action by diazoxide.28 NBD2 is possibly involved in the ADP-dependent activation by diazoxide, and the SUR2A-type C-terminal tail (C42) inhibits it. Tetsuro Matsuoka et al. Circ Res. 2000;87: Copyright © American Heart Association, Inc. All rights reserved.


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