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The Voltage Gates of Connexin Channels are Sensitive to CO_2

机译:连接蛋白通道的电压门对CO_2敏感

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Cx45 channel sensitivity to CO_2, transjunctional voltage (V_j) and inhibition of calmodulin (CaM) expression was tested in oocytes by dual voltage-clamp. Cx45 channels are very sensitive to V_j and close preferentially by the slow gate, likely the same as the chemical gate. With CO_2-induced drop in junctional conductance (G_j), the speed of V_j-dependent inactivation of junctional current (I_j) and V_j sensitivity increased. With 40 mV V_j, the τ of single exponential I_j decay reversibly decreased by ~40% with CO_2, and G_(j steady state)/G_(j peak) decreased multiphasically, indicating that kinetics and V_j sensitivity of chemical/slow-V_j gating are altered by changes in [H~+]_i and/or [Ca~(2+)]_i. With 15 min exposure to CO_2, G_j dropped to 0% in controls and by ~17% following CaM expression inhibition; similarly, V_j sensitivity decreased significantly. This indicates that the speed and sensitivity of V_j-dependent inactivation of Cx45 channels are increased by CO_2, and that CaM plays a role in gating. Cx32 channels behaved similarly, but the drop in both G_(j steady state)/G_(j peak) and τ with CO_2 matched more closely that of G_(j peak). In contrast, sensitivity and speed of V_j gating of Cx40 and Cx26 channels decreased, rather than increased, with CO_2 application.
机译:通过双电压钳测试了卵母细胞中Cx45通道对CO_2的敏感性,跨结电压(V_j)和钙调蛋白(CaM)表达抑制。 Cx45通道对V_j非常敏感,并优先通过慢速门关闭,可能与化学门相同。随着CO_2诱导的结电导(G_j)下降,依赖于V_j的结电流(I_j)失活的速度和V_j的灵敏度增加。 V_j为40 mV时,CO_2时单指数I_j衰减的τ可逆地降低约40%,G_(j稳态)/ G_(j峰值)呈多相下降,表明化学/慢V_j门控的动力学和V_j敏感性通过[H〜+] _ i和/或[Ca〜(2 +)] _ i的更改来更改。暴露于CO_2 15分钟后,对照中的G_j降至0%,CaM表达抑制后G_j降低约-17%。同样,V_j灵敏度显着下降。这表明CO_2增加了Vxj依赖的Cx45通道失活的速度和灵敏度,并且CaM在门控中起作用。 Cx32通道的行为类似,但是G_(j稳态)/ G_(j峰值)和τ随CO_2的下降更接近G_(j峰值)。相反,随着CO_2的应用,Cx40和Cx26通道的V_j门控的灵敏度和速度降低而不是提高。

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