Related Experiment Video
Updated: Apr 22, 2026
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Sepsis varies arterial two-pore-domain potassium channel messenger RNA in mice
Florian Bieling1, Florian Uhle1, Katja Weissmüller1
1Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig-University, Giessen, Germany.
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.
Insights
Sepsis alters the expression of two-pore potassium (K2P) channels and dopamine receptors in mesenteric arterioles, potentially explaining reduced blood flow and organ dysfunction during sepsis.
Area of Science:
- Physiology
- Molecular Biology
- Sepsis Pathophysiology
Background:
- Sepsis-induced hemodynamic changes, particularly microcirculatory dysfunction in mesenteric arterioles, lead to organ failure.
- Impaired splanchnic perfusion can compromise intestinal barrier integrity, promoting bacterial translocation and systemic infection.
- Two-pore potassium (K2P) channels regulate vascular tone and are sensitive to inflammatory mediators during sepsis.
- Dopamine receptors (D1R and D2R) are implicated in arterial tone regulation under hypoxic conditions.
Purpose of the Study:
- To investigate the expression of K2P channels and dopamine receptors in mesenteric arterioles during sepsis.
- To determine the role of these channels and receptors in sepsis-induced hypoperfusion.
Main Methods:
- Sepsis was induced in mice using the cecal ligation and puncture model.
- Real-time polymerase chain reaction (PCR) was used to analyze RNA expression of K2P channels and dopamine receptors.
- Western blotting was employed to assess protein levels of specific K2P channels.
Main Results:
- Sepsis differentially affected K2P channel RNA levels: TWIK-related acid-sensitive K+ channel 1 and 2 (TASK 1, TASK 2) and TWIK-related K+ channel 1 (TREK 1) were downregulated, while TWIK 2 was unaffected.
- Dopamine receptor 1 (D1R) RNA levels decreased, whereas dopamine receptor 2 (D2R) RNA levels increased during sepsis.
- Changes in K2P channel and dopamine receptor expression were observed at the RNA level.
Conclusions:
- The observed alterations in K2P channel and dopamine receptor expression are potential contributors to reduced mesenteric perfusion in sepsis.
- These molecular changes may play a significant role in the pathophysiology of sepsis-induced organ dysfunction.
