Systemic lipopolysaccharide stimulates airway transepithelial Na+ transport by increasing ENaC and Na+,K+ -pump activity

Our laboratory found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V t) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. We hypothesized that LPS stimulates the transepithelial movement of Na+ via the epithelial sodium channel (ENaC)/Na+,K+-pump axis, leading to hyperpolarization of Vt. LPS increased the Vt response to amiloride, i.e., offset the effect of LPS, indicating that Na+ transport was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na+,K+-pump with basolateral amphotericin B. LPS had no effect on the hyperpolarization response to apical trypsin in the Ussing chamber, indicating that channel activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na+,K +-pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater Vt in the presence of amphotericin B in tracheas from LPS-treated animals compared to controls revealed that LPS increased Na+,K+-pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na+,K+-pump via extracellular K+ removal, loading the epithelium with Na +, and observing a greater hyperpolarization response to K + restoration. Using qPCR, the effects of LPS on the transcription of alphaENaC, alpha1 Na+,K+-pump, COX-2, eNOS, iNOS, IL-1beta, and TNF-alpha were measured at 3 and 18 h. In the epithelium, LPS increased the transcription of COX-2, IL-1beta, and, to nonsignificant extent, TNF-alpha at 3 h, but not at 18 h. In alveolar macrophages, TNF-alpha, and, to a nonsignificant extent, COX-2 and IL-1beta were up-regulated at 3 h, but not at 18 h. Even though LPS stimulated the transcription of some genes, alphaENaC and alpha1 Na +,K+-ATPase transcription were not affected. The expression of alpha-, beta-, and gamma-ENaC and alpha1 Na+,K+-pump from tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the alpha1 subunit and the alpha 1-, alpha2-, and alpha3-subunits, collectively, of the Na+,K+-pump. Taken together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na+,K+-pump. ENaC activation by LPS is not accomplished via a change in ENaC regulation involving proteolytic cleavage. LPS increases Na+ transport downstream of the genetic level, in part, by stimulating the expression of the Na+,K+-pump

Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7