A mutation in the beta interaction domain of the Ca(2+) channel alpha(1C) subunit reduces the affinity of the (+)-[(3)H]isradipine binding site.
The molecular mechanisms of how alpha(1) and beta subunits of voltage-gated Ca(2+) channels interact with one another are still controversial. Here we show that despite a mutation in the beta interaction domain that has previously been shown to disrupt binding, alpha(1C)Y467S and beta(1a-myc) still formed immunoprecipitable complexes when coexpressed in tsA201 cells. However, the alpha(1C)Y467S-beta(1a-myc) complexes had a decreased affinity to (+)-[(3)H]isradipine. This indicates that the beta interaction domain in the I-II loop of the alpha(1) subunit is not merely an anchor required for the functional interaction of the two Ca(2+) channel subunits but is itself part of the effector pathway for beta-induced channel modulation.
Department of Biochemical Pharmacology, University of Innsbruck, A-6020 Innsbruck, Austria.
Monika
M
Hitzl
Jörg
J
Striessnig
Birgit
B
Neuhuber
Bernhard E
BE
Flucher
D001483:Base Sequence; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D017275:Isradipine / Q000378:metabolism*; D009154:Mutation; D011233:Precipitin Tests; D011869:Radioligand Assay; D014316:Tritium
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017931:DNA Primers; D014316:Tritium; D017275:Isradipine