BETA-SUBUNIT HETEROGENEITY IN NEURONAL L-TYPE CA2+ CHANNELS

Heterologous expression studies have shown that the activity of voltag e-gated Ca2+ channels is regulated by their beta subunits in a beta su bunit isoform-specific manner, In this study we therefore investigated if one or several beta subunit isoforms associate with L-type Ca2+ ch annels in different regions of mammalian brain, All four beta subunit isoforms (beta 1b, beta 2, beta 3, and beta 4) are expressed in cerebr al cortex as shown in immunoblots, Immunoprecipitation of (+)-[H-3]isr adipine-labeled L-type channels revealed that the majority of beta sub unit-associated L-type channels was associated with beta 3 (42 +/- 8%) and beta 4 (42 +/- 7%) subunits, whereas beta 1b and beta 2 were pres ent in a smaller fraction of channel complexes, beta 3 and beta 4 were also the major L-type channel beta subunits in hippocampus. In cerebe llum beta 1b, beta 2, and beta 3 but not beta 4 subunits were expresse d at lower levels than in cortex, Accordingly, beta 4 was the most pro minent beta subunit in cerebellar L-type channels, This beta subunit c omposition was very similar to the one determined for I-125-omega-cono toxin-GVIA-labeled N-type and I-I25-omega-conotoxin-MVIIC-labeled P/Q- type channel complexes in cerebral cortex and cerebellum, Our data sho w that all four beta subunit isoforms associate with L-type Ca2+ chann els in mammalian brain, This beta subunit heterogeneity may play an im portant role for the fine tuning of L-type channel function and modula tion in neurons.