Dysfunction and overexpression of ENaC-mediated sodium influx exacerbates activation of NLRP3-inflammasome mediated inflammation in cells with CF-associated mutations and is modulated by inhibition of these amiloride-sensitive sodium (Na+) channels.
CFTR modulators have potent innate anti-inflammatory properties that can be measured in clinic, both ex vivo and in vitro, which can be used to predict treatment efficacy.
Aqueous solubility of cystic fibrosis drug ivacaftor is ~200-fold lower, whereas the potency of its stimulatory effect on the CFTR channel is >100-fold higher, than reported, and is fully reversible.
Analysis of the mechanism of action of cystic fibrosis corrector drugs reveals signalling pathways potently controlling the proteostasis of the main disease-relevant CFTR mutant.
Coupling of CFTR pore opening to nucleotide binding domain dimerization does not depend on ATP binding, but is an inherent property of the channel protein and likely other ABC transporters.
Tannic acid acts as an ‘antidote’ against the negative effects of a bacterial enzyme, which can both aggravate cystic fibrosis and enable the anthrax bacteria to evade the immune responses elicited by a typical live vaccine.
In the CFTR chloride channel, ATP bound in the catalytic site promotes pore opening, whereas ATP bound in the non-catalytic site supports unidirectional conformational cycling by preventing pore closure without ATP hydrolysis in the catalytic site.
Loss of an amino acid transporter and tissue depletion of nitric oxide worsens the intestinal function of CF mice, a finding that potentially explains variation in disease severity amongst CF individuals.
