ABCMdb

ABCC7 p.Arg303Glu

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Publications

PMID: 17043152 [PubMed] Aubin CN et al: "Positive charges at the intracellular mouth of the pore regulate anion conduction in the CFTR chloride channel."

No. Sentence Comment

7 However, the very low conductance of both R303E and R352E-CFTR could be greatly increased by elevating intracellular Cl-concentration. Login to comment
43 In contrast to wild-type CFTR, mutants R303E and, to a lesser extent, R352E showed outward rectification of the I-V relationship with symmetrical 154 mM Cl- solutions. Login to comment
63 In contrast, both R303E and R352E were associated with strong outward rectification (Fig. 2 A), which is quantified in Fig. 2 B. Login to comment
71 As shown in Fig. 3 B, macroscopic I-V rectification was indeed highly sensitive to symmetrical Cl-concentration in both R303E and R303Q, suggesting that increasing the Cl-concentration partially reverses the effects of removing these positive charges. Login to comment
75 (B) The degree of rectification in R303E, R303Q, and R352Q is dependent on the Cl- concentra- tion. Login to comment
95 (B) Mean single channel current-voltage relationships constructed from such recordings for wild type (■), R303E (●) and R352E (○). Login to comment
100 Single channel currents carried by R303E and R352E under the same symmetrical Cl- solutions used in Fig. 2 are shown in Fig. 5 A. Login to comment
103 For example, at -80 mV, single channel current amplitude was reduced by 89 ± 0% (n = 4) in R303E and by 75 ± 2% (n = 3) in R352E, while at +80 mV, unitary currents were reduced by 30 ± 1% (n = 4) in R303E and by 25 ± 1% (n = 4) in R352E (Fig. 5 B). Login to comment
104 The Cl-dependence of I-V shape in R303E and R352E is consistent with removal of positive surface charges that normally act to increase the Cl-concentration at the inner mouth of the pore. Login to comment
114 (A) Example single channel currents recorded from wild type, R303E, and R352E at different intracellular Cl- concentrations (154 or 304 mM, as indicated), at a membrane potential of -20 mV. For each trace, the line to the left represents the current level when the channel is closed. Login to comment
126 The results of these experiments are summarized in Fig. 9. Modification of the introduced cysteine residue by negatively charged MTSES leads to pronounced outward rectification, similar to that seen in R303E (Fig. 2 B) and consistent with the deposition of a negative charge at the inner mouth of the pore, while modification by positively charged MTSET resulted in a wild type-like, moderately inwardly rectified I-V relationship. Login to comment
149 Under these conditions, current carried not only by wild-type CFTR, but also by each of the channel mutants R303E, R352E (Fig. 10), R80E, R242E, R933E, R1102E, and R352Q (not depicted) showed reversal potentials that were not significantly different from the calculated Cl- equilibrium potential (+33.4 mV). Login to comment
184 Furthermore, rectification in R303Q and R303E appeared more sensitive to the intracellular Cl-concentration than in R352Q and R352E (Fig. 3 B). Login to comment
196 Unfortunately we were unable to obtain single channel recordings at Cl- concentrations higher than 304 mM; however, the dramatic increase in conductance seen in both R303E and R352E when intracellular [Cl-] was increased from 154 to 304 mM (Fig. 6) suggests that the conductance of these mutant channels is far from saturated at this elevated Cl-concentration, consistent with a large increase in Km. Login to comment
199 Nevertheless, unitary currents carried by Cl- influx were also reduced in both R303E and R352E (Fig. 5). Login to comment
208 R134Q is associated with outward rectification (Fig. 10, A and B); however, this effect shows a complex Cl-dependence that, unlike that of R303E, R303Q, and R352Q (Fig. 3 B), is not consistent with a simple surface charge effect. Furthermore, R134Q shows an extremely small apparent unitary conductance (Fig. 10 C). Login to comment

PMID: 17293558 [PubMed] St Aubin CN et al: "Identification of a second blocker binding site at the cytoplasmic mouth of the cystic fibrosis transmembrane conductance regulator chloride channel pore."

No. Sentence Comment

97 The greatest weakening of inhibition was observed in the side chain charge-reversing R303E mutant, whereas the Fig. 4. Login to comment