ABCMdb

ABCC7 p.Val345His

None has been submitted yet.

Publications

PMID: 23083715 [PubMed] El Hiani Y et al: "Tuning of CFTR chloride channel function by location of positive charges within the pore."

No. Sentence Comment

78 As shown in Fig. 5, block of both I344H and V345H by Pt(NO2)4 2 was drastically stronger at pH 5.5 than at pH 9.0, with the mean Kd(0) for I344H and V345H being ~13-fold and ~38-fold lower, respectively, at acid pH (Fig. 5 D). Login to comment
80 In contrast to these large effects of pH on block by Pt(NO2)4 2 , the single-channel conductance of I344H and V345H, as well as that of the WT, were not significantly different at pH 5.5 and pH 9.0 (Fig. 6). Login to comment
81 Whereas the conductance of V345H was reduced to ~80% of WT conductance (independently of pH), the conductance of I344H was not significantly different from that of the WT (Fig. 6 C). Login to comment
82 Interestingly, whereas the conductance of I344H (at pH 5.5) was not significantly different from that of I344K (p > 0.37; Fig. 2 C), the conductance of V345H (pH 5.5) was ~20% greater than that of V345K (p < 0.002). Login to comment
102 In fact, the results of Fig. 6 support the latter explanation, because specifically toggling the positive charge in I344H or V345H by changing the pH did not alter single-channel conductance. Login to comment
103 Furthermore, the notion that charge is not the only factor that influences conductance is supported by the fact that the conductance of V345K was significantly less than that of V345H when measured at pH 5.5, where the histidine side chain is expected to bear a positive charge. Login to comment
128 (A) Example leak-subtracted macroscopic I/V relationships for V345H at intracellular pH of 5.5 (left) or 9.0 (right, different patch). Login to comment
130 (B) Mean concentration-inhibition relationships for WT (circles), I344H (squares), and V345H (triangles) at intracellular pH 5.5 (left, solid symbols) or 9.0 (right, open symbols) at a membrane potential of 100 mV. Each relationship was fitted according to Eq. 1. Login to comment
138 (A) Example single-channel currents carried by V345H at a membrane potential of 50 mV, at a bath pH of 5.5 (left) or 9.0 (right, different patch). Login to comment
140 (B) Mean single-channel i/V relationships for WT and V345H under these two pH conditions. Login to comment
148 At these two sites, the effect on Pt(NO2)4 2 block could be ascribed unambiguously to an effect of the introduced positive charge, because the mutants I344H and V345H showed Pt(NO2)4 2 block similar to that of WT at pH 9.0, where the histidine side chains are expected to be uncharged, whereas at pH 5.5, which should promote protonation of these side chains, Pt(NO2)4 2 block was drastically strengthened (Fig. 5). Login to comment