A POTENTIAL SITE OF FUNCTIONAL MODULATION BY PROTEIN-KINASE-A IN THE CARDIAC CA2+ CHANNEL ALPHA(1C) SUBUNIT

The well-characterized enhancement of the cardiac Ca2+ L-type current by protein kinase A (PKA) is not observed when the corresponding chann el is expressed in Xenopus oocytes, possibly because it is fully phosp horylated in the basal state. However, the activity of the expressed c hannel is reduced by PKA inhibitors. Using this paradigm as an assay t o search for PKA sites relevant to channel modulation, rye have found that mutation of serine 1928 of the alpha(1C) subunit to alanine aboli shes the modulation of the expressed channel by PKA inhibitors. This e ffect was independent of the presence of the beta subunit, Phosphoryla tion of serine 1928 of alpha(1C) may mediate the modulatory effect of PKA on the cardiac voltage-dependent Ca2+ channel.