| Summary: | Activation of a5??1 integrin potentiates L-type calcium current in vascular smooth
muscle, which is partly mediated by tyrosine phoshorylation of the a1c channel subunit.
Expressed rabbit VSM and neuronal isoforms are also potentiated by a5??1 integrin
activation and require dual phosphorylation of a1c by PKA and c-Src. To explore
common mechanisms of regulation by a5??1 integrin, whole cell patch clamp experiments
were used to investigate the effects of a5??1 integrin antibody on expressed cardiac
calcium channels. In HEK cells transfected with a1c, ??2a and a2-d1 subunits alone,
currents increased 1.8 ?? 2.0 fold on application of a5??1 antibody. The potentiation was
almost completely abolished on the application of PKI, a highly specific Protein Kinase
A (PKA) inhibitor. The expressed currents increased 2.0 ?? 2.2 fold on application of
PKA activator 8-Br-cAMP, and abolished by PKI. Our results suggest that regulation of
L-type calcium channels by a5??1 integrin is a general mechanism shared by VSM,
neuronal and cardiac channels. However, in the cardiac isoform, only PKA
phosphorylation is involved.
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