Publication: Mapping of dihydropyridine binding residues in a less sensitive invertebrate L-type calcium channel (LCav 1)
All || By Area || By Year| Title | Mapping of dihydropyridine binding residues in a less sensitive invertebrate L-type calcium channel (LCav 1) | Authors/Editors* | Senatore A, Boone A, Lam S, Dawson TF, Zhorov B, Spafford J. |
|---|---|
| Where published* | Channels (Austin) |
| How published* | Journal |
| Year* | 2011 |
| Volume | 5 |
| Number | 3 |
| Pages | 173-87 |
| Publisher | |
| Keywords | |
| Link | http://www.ncbi.nlm.nih.gov/pubmed/21487241 |
| Abstract |
Invertebrate L-type calcium channel, LCav 1, isolated from the pond snail Lymnaea stagnalis is nearly indistinguishable from mammalian Cav 1.2 (α1C) calcium channel in biophysical characteristics observed in vitro. These L-type channels are likely constrained within a narrow range of biophysical parameters to perform similar functions in the snail and mammalian cardiovascular systems. What distinguishes snail and mammalian L-type channels is a difference in dihydropyridine sensitivity: 100 nM isradipine exhibits a significant block of mammalian Cav 1.2 currents without effect on snail LCav 1 currents. The native snail channel serves as a valuable surrogate for validating key residue differences identified from previous experimental and molecular modeling work. As predicted, three residue changes in LCav 1 (N_3o18, F_3i10, and I_4i12) replaced with DHP-sensing residues in respective positions of Cav 1.2, (Q_3o18, Y_3i10, and M_4i12) raises the potency of isradipine block of LCaV 1 channels to that of mammalian Cav 1.2. Interestingly, the single N_3o18_Q mutation in LCav 1 channels lowers DHP sensitivity even further and the triple mutation bearing enhanced isradipine sensitivity, still retains a reduced potency of agonist, (S)-Bay K8644. |
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