Calcium functions as an essential second messenger during neuronal development and synapse acquisition. Voltage-dependent calcium channels (VDCC), which are critical to these processes, are heteromultimeric complexes composed of ␣ 1 , ␣ 2 /␦, and ␤ subunits. ␤ subunits function to direct the VDCC complex to the plasma membrane as well as regulate its channel properties. The importance of ␤ to neuronal functioning was recently underscored by the identification of a truncated ␤4 isoform in the epileptic mouse lethargic ( These results suggested that subsequent maturation of ␣ 1B or its assembly with auxiliary subunits was required to exhibit high affinity 125 I-CTX binding. The temporal pattern of expression of ␤ subunits and their assembly with ␣ 1B indicated a developmental pattern of expression of ␤ isoforms: ␤1b increased 3-fold from P0 to adult, ␤4 increased 10-fold, and both ␤2 and ␤3 expression remained unchanged. As the ␤ component of N-type VDCC changed during postnatal development, we were able to identify both immature and mature forms of N-type VDCC. At P2, the relative contribution of ␤ is ␤1b > ␤3 > > ␤2, whereas at P14 and adult the distribution is ␤3 > ␤1b ‫؍‬ ␤4. Although we observed no ␤4 associated with the ␣ 1B at P2, ␤4 accounted for 14 and 25% of total ␣ 1B /␤ subunit complexes in P14 and adult, respectively. Thus, of the ␤ isoforms analyzed, only the ␤4 was assembled with the rat ␣ 1B to form N-type VDCC with a time course that paralleled its level of expression during rat brain development. These results suggest a role for the ␤4 isoform in the assembly and maturation of the N-type VDCC.

Voltage-gated calcium channels (VDCC) are essential to neuronal maturation and differentiation. It is believed that important signaling information is encoded by VDCC-mediated calcium influx that has both spatial and temporal components. VDCC are multimeric complexes comprised of a pore-forming alpha1 subunit and auxiliary beta and alpha2/delta subunits. Changes in the fractional contribution of distinct calcium conductances to the total calcium current have been noted in developing and differentiating neurons. These changes are anticipated to reflect the differential expression and localization of the pore-forming alpha1 subunits. However, as in vitro studies have established that beta regulates the channel properties and targeting of alpha1, attention has been directed toward the developmental expression and assembly of beta isoforms. Recently, changes in the beta component of the omega-conotoxin GVIA (CTX)-sensitive N-type VDCC have indicated differential assembly of alpha1B with beta in postnatal rat brain. In addition, unique properties of beta4 have been noted with respect to its temporal pattern of expression and incorporation into N-type VDCC complexes. Therefore, the expression and assembly of specific alpha1/beta complexes may reflect an elaborate cellular strategy for regulating VDCC diversity. The importance of these developmental findings is bolstered by a recent study which identified mutations in the beta4 as the molecular defect in the mutant epileptic mouse (lethargic; lh/lh). As beta4 is normally expressed in both forebrain and cerebellum, one may consider the impact of the loss of beta4 upon VDCC assembly and activity. The importance of the beta1b and beta4 isoforms to calcium channel maturation and assembly is discussed.