ABCMdb

PMID: 17397825

Zhou JJ, Linsdell P
Molecular mechanism of arachidonic acid inhibition of the CFTR chloride channel.
Eur J Pharmacol. 2007 Jun 1;563(1-3):88-91. Epub 2007 Mar 3., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Lys95Gln ABCC7 p.Arg303Gln Charge-neutralizing mutants K95Q and R303Q both increased the Kd for inhibition from ~3.5 bc;M in wild type to ~17 bc;M. Login to comment 35 ABCC7 p.Lys95Gln ABCC7 p.Arg303Gln As also shown in Fig. 1, inhibition by arachidonic acid is dramatically weakened by point mutations which remove important positive charges from the pore inner vestibule, K95Q and R303Q, leading to approximately a 5-fold increase in Kd in both cases. Login to comment 38 ABCC7 p.Lys95Arg ABCC7 p.Arg303Lys Thus, while the charge conservative K95R and R303K mutations were not associated with a significant increase in Kd (PN0.3, two-tailed t-test) all mutations which neutralized or reversed either of these two positive charges were associated with a significant increase in Kd (Fig. 2). Login to comment 44 ABCC7 p.Lys95Gln ABCC7 p.Arg303Gln (A) Example leak-subtracted current-voltage relationships recorded from inside-out membrane patches for wild type, K95Q, and R303Q-CFTR. Login to comment 46 ABCC7 p.Lys95Gln ABCC7 p.Arg303Gln (B) Mean fraction of control current remaining (I/I0) after the addition of different concentrations of arachidonic acid at a membrane potential of -100 mV, for wild type (cf;), K95Q (cb;) and R303Q (bc;). Login to comment 48 ABCC7 p.Lys95Gln ABCC7 p.Arg303Gln In each case the fitted lines are to Eq. (1), giving a Kd of 3.5 bc;M and nH of 1.54 for wild type, Kd of 17.2 bc;M and nH of 0.77 for K95Q, and Kd of 16.5 bc;M and nH of 1.06 for R303Q. Login to comment