Differential Expression and Association of Calcium Channel α1B and β Subunits during Rat Brain Ontogeny

Abstract

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.

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

“…Indeed, activation of PKA was shown to antagonize ethanol modulation of N-and P/Q-type VGCCs in PC12 cells (Solem et al, 1997). N-type channel subunit composition modifications during development could be an additional explanation for the different sensitivity to ethanol throughout maturation (Jones et al, 1997;Vance et al, 1998;Lin et al, 1999;Pan and Lipscombe, 2000) Our findings are consistent with several reports indicating that these channels are important targets of ethanol. Through their modulation, ethanol inhibits dopamine release from rat striatal synaptosomes (Woodward et al, 1990), vasopressin release from rat neurohypophysial nerve terminals (Wang et al, 1991), and depolarization-induced rises in [Ca 2ϩ ] i in PC12 cells (Solem et al, 1997).…”

Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells

“…Insulin-secreting cell lines express functional N-type Ca 2ϩ channels, which are important for insulin secretion (17,43); however, it has not been clearly established whether primary pancreatic ␤-cells express this type of channel, and their role in the glucose-induced insulin secretion is still under debate (12,22,34,43,45). We observed expression of ␣1B mRNA and their proteins in neonatal and adult ␤-cells.…”

“…Neurons and myocytes exhibit a changing pattern of Ca 2ϩ channel expression during development (19,24,31,45). This type of regulation has not been previously reported in pancreatic ␤-cells, and it is interesting because it could be related to the functional maturation of ␤-cells.…”

Inhibition of Recombinant N-Type CaVChannels by the γ2Subunit Involves Unfolded Protein Response (UPR)-Dependent and UPR-Independent Mechanisms

“…Given that the Ca V ␥ 2 /␥ 3 subunits significantly decrease N-type channel activity and expression, they might provide a negative feedback on current amplitude and neurotransmission. In addition, it has been reported that N-type channel expression is an important cue in the genesis of synaptic transmission (Jones et al, 1997;Vance et al, 1998). Therefore, it is also possible that Ca V ␥ 2 /␥ 3 might play a role as a negative regulator for N-type channel expression during brain ontogeny.…”