UNIQUE REGULATORY PROPERTIES OF THE TYPE 2A CA2-SUBUNIT CAUSED BY PALMITOYLATION( CHANNEL BETA)

beta subunits of voltage-gated Ca2+ channels are encoded in four genes and display additional molecular diversity because of alternative spl icing. At the functional level, all forms are very-similar except for beta 2a, which differs in that it does not support prepulse facilitati on of alpha(1C) Ca2+ channels, inhibits voltage-induced inactivation o f neuronal alpha(1E) Ca2+ channels, and is more effective in blocking inhibition of alpha(1E) channels by G protein-coupled receptors. We sh ow that the distinguishing properties of beta 2a, rather than interact ion with a distinct site of alpha(1), are because of the recently desc ribed palmitoylation of cysteines in positions three and four, which a lso occurs in the Xenopus oocyte. Essentially, all of the distinguishi ng features of beta 2a were lost in a mutant that could not be palmito ylated [beta 2a(Cys(3,4)Ser)]. Because protein palmitoylation is a dyn amic process, these findings point to the possibility that regulation of palmitoylation may contribute to activity-dependent neuronal and sy naptic plasticity. Evidence is presented that there may exist as many as three beta 2 splice variants differing only in their N-termini.