Inhibition of histone deacetylase (HDAC) by 4-phenylbutyrate results in increased junctional conductance between rat corpora smooth muscle cells

4-苯基丁酸抑制组蛋白去乙酰化酶 (HDAC) 导致大鼠海绵体平滑肌细胞之间的连接传导增加

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作者:Hong Zhan Wang, Barbara Rosati, Chris Gordon, Virginijus Valiunas, David McKinnon, Ira S Cohen, Peter R Brink

Abstract

4-phenylbutyrate (4-PB) has been shown to increase the protein content in a number of cells types. One such protein is Connexin43 (Cx43). We show here that 4-phenylbutyrate exposure results in significantly elevated cell to cell coupling, as determined by dual whole cell patch clamp. Incubation with 5 mM 4PB for 24 h or more nearly doubles junctional conductance. Interestingly, mRNA levels for Cx43 declined with exposure to 4-PB while western blot analysis revealed not significant change in protein levels. These data are most consistent with stabilization of the existing Cx43 pool or alterations in the number of functional channels within an existing pool of active and silent channels. These data represent a baseline for testing the efficacy of increased connexin mediated coupling in a variety of multicellular functions including erectile function.

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