Vacassenno Rachael M, Haddad Christine N, Cooper Robin L
Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA; Department of Biology, Eastern Kentucky University, Richmond, KY 40475, USA.
Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2023 Apr;266:109571. doi: 10.1016/j.cbpc.2023.109571. Epub 2023 Feb 4.
Exposure of Drosophila skeletal muscle to bacterial lipopolysaccharides (LPS) rapidly and transiently hyperpolarizes membrane potential. However, the mechanism responsible for hyperpolarization remains unclear. The resting membrane potential of the cells is maintained through multiple mechanisms. This study investigated the possibility of LPS activating calcium-activated potassium channels (K) and/or K2p channels. 2-Aminoethyl diphenylborinate (2-APB), blocks uptake of Ca into the endoplasmic reticulum (ER); thus, limiting release from ryanodine-sensitive internal stores to reduce the function of K channels. Exposure to 2-APB produces waves of hyperpolarization even during desensitization of the response to LPS and in the presence of doxapram. This finding in this study suggests that doxapram blocked the acid-sensitive K2p tandem-pore channel subtype known in mammals. Doxapram blocked LPS-induced hyperpolarization and depolarized the muscles as well as induced motor neurons to produce evoked excitatory junction potentials (EJPs). This was induced by depolarizing motor neurons, similar to the increase in extracellular K concentration. The hyperpolarizing effect of LPS was not blocked by decreased extracellular Caor the presence of Cd. LPS appears to transiently activate doxapram sensitive K2p channels independently of K channels in hyperpolarizing the muscle. Septicemia induced by gram-negative bacteria results in an increase in inflammatory cytokines, primarily induced by bacterial LPS. Currently, blockers of LPS receptors in mammals are unknown; further research on doxapram and other K2p channels is warranted. (220 words).
将果蝇骨骼肌暴露于细菌脂多糖（LPS）中会迅速且短暂地使膜电位超极化。然而，超极化的机制仍不清楚。细胞的静息膜电位通过多种机制维持。本研究调查了LPS激活钙激活钾通道（K）和/或K2p通道的可能性。2-氨基乙基二苯基硼酸盐（2-APB）可阻止Ca进入内质网（ER）；因此，限制了从兰尼碱敏感的内部储存库中的释放，以降低K通道的功能。即使在对LPS的反应脱敏期间以及存在多沙普仑的情况下，暴露于2-APB也会产生超极化波。本研究中的这一发现表明，多沙普仑阻断了哺乳动物中已知的酸敏感K2p串联孔通道亚型。多沙普仑阻断了LPS诱导的超极化，使肌肉去极化，并诱导运动神经元产生诱发兴奋性接头电位（EJP）。这是由运动神经元去极化诱导的，类似于细胞外K浓度的增加。LPS的超极化作用不会被细胞外Ca的减少或Cd的存在所阻断。LPS似乎在使肌肉超极化时独立于K通道短暂激活多沙普仑敏感的K2p通道。革兰氏阴性菌引起的败血症会导致炎症细胞因子增加，主要由细菌LPS诱导。目前，哺乳动物中LPS受体的阻滞剂尚不清楚；有必要对多沙普仑和其他K2p通道进行进一步研究。
