KCNQ1 K⁺ Channels are Involved in Lipopolysaccharide-induced Apoptosis of Distal Kidney Cells

Abstract

Most bacteria initiate host inflammatory responses through interactions with epithelial cells. Lipopolysaccharide (LPS), a component of the bacterial cell wall is a major cause of septic shock in emergency care units and in the pathogenesis of acute renal failure. Kidney cells exposed to LPS undergo apoptotic changes, including cell volume decrease, phosphatidylserine exposure, caspase-3- and membrane K⁺ conductance -activation. Whole-cell configuration was used to identify K⁺ channels in primary and immortalized culture of mice distal convoluted tubules. LPS exposure induced a 3 fold increase in intracellular cAMP concentration and the activation of an outwardly rectifying K⁺ conductance in both immortalized and primary culture of distal cells. This LPS-induced current exhibited KCNQ1 K⁺ channel characteristics, i.e. inhibition by quinidine, chromanol293B and low dose of HMR1556 (IC50<1 µM) and insensitive to TEA and charybdotoxin. The background-like biophysical properties of the current suggest that the KCNQ1 pore-forming subunit is associated with a KCNE2 or KCNE3 ancillary subunit. RT-PCR experiments confirmed the presence of KCNQ1 and KCNE3 mRNA transcripts in primary culture of distal segments. Activation of the KCNQ1/KCNE3 K⁺ current appeared to be an essential step in the LPS-induced apoptosis process since HMR1556 blocked the LPS-induced- cell volume decrease, -caspase-3 activation and -phosphatidylserine exposure.

Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury

“…Several studies have observed a number of apoptotic tubular cells in LPS-induced acute kidney injury [37][38][39]. Indeed, VitD3 has an anti-apoptotic activity [40,41].…”

Comparison of Mouse Urinary Metabolic Profiles after Exposure to the Inflammatory Stressors γ Radiation and Lipopolysaccharide

“…Moreover, both stressors elicit injury in various tissues. LPS can activate K+ channels, leading to ion perturbation, increased intracellular cAMP, and apoptosis in kidney cells (8, 33), whereas increased intracellular cAMP in immune cells protects against DNA damage-induced apoptosis (34). Although it has been reported in the literature that radiation is able to detoxify LPS by destruction of the polysaccharide moieties and alteration of the lipid A component (35), the doses required far exceed what would be likely encountered in a radiological event.…”

“…However, similar symptoms may be due to other factors. During infections, bacterial toxins, in particular lipopolysaccharide (LPS), have been demonstrated to induce nausea, vomiting and diarrhea, leading to acute renal failure, septic shock and death (8-11). LPS is found in the outer wall of Gram-negative bacteria, acts as an endotoxin, and elicits immune responses in animals by activating innate immune responses and triggering secretion of pro-inflammatory cytokines in various cells types (11-13).…”

Basolateral membrane K+channels in renal epithelial cells

“…Interestingly, Duranton et al (27) identified the ␤-subunit KCNE3 within cultured mouse DCT cells. Furthermore, they examined the involvement of KCNQ1-KCNE3 in the LPSinduced apoptosis of mouse DCT cells and revealed there is an activation of KCNQ1-KCNE3 conductance by LPS.…”