Sepsis varies arterial two-pore-domain potassium channel messenger RNA in mice

Background: Hemodynamic changes are mainly responsible for organ failure and subsequently for the poor outcome of sepsis. Occurring macro- and micro-circulatory dysfunctions are not homogeneously distributed in the vessel beds. Especially mesenteric arterioles are subject to hypoperfusion during sepsis, and in consequence, a dysfunction of the downstream organs develops. Furthermore, impaired perfusion of the splanchnic area may cause intestinal barrier breakdown supporting the translocation of bacteria or toxins into the circulation aggravating a systemic infection and organ failure. The two-pore potassium channels (K2P channels) are responsible for setting the resting membrane potential of smooth muscle cells. Because of their sensitivity by various metabolic or humoral mediators, which are also varying during inflammatory processes, they can determine vascular resistance during sepsis. Dopamine receptors type 1 (D1R) and 2 (D2R) are assumed to be involved in the regulation of arterial tone under hypoxic conditions and are investigated too. Materials and methods: Sepsis was induced in mice by the cecal ligation and puncture model. This study investigates the expression of K2P channels and the dopamine receptors at RNA level by real-time polymerase chain reaction analysis and two K2P channels at the protein level by Western blotting. Results: The RNA levels of K2P channels respond differently to sepsis. Although the weakly inward rectifying K+ channel 2 (TWIK 2) is not affected, TWIK-related acid-sensitive K+ channel 1 and 2 (TASK 1 and TASK 2) and TWIK-related K+ channel 1 (TREK 1) are partially downregulated during the course of the experiment. A downregulation of D1R and an upregulation of the D2R could be observed during the septic phase. Conclusions: The changes shown could be important factors for the reduced mesenteric perfusion during sepsis. (C) 2015 Elsevier Inc. All rights reserved.