Influx of calcium through voltage-dependent channels regulates processes throughout the nervous system. Specifically, influx through L-type channels plays a variety of roles in early neuronal development and is commonly modulated by G-protein-coupled receptors such as GAB A B receptors. Of the four isoforms of L-type channels, only C a V 1.2 and C a V 1.3 are predominately expressed in the nervous system. Both isoforms are inhibited by the same pharmacological agents, so it has been difficult to determine the role of specific isoforms in physiological processes. In the present study, Western blot analysis and confocal microscopy were utilized to study developmental expression levels and patterns of C a V 1.2 and C a V 1.3 in the CA1 region of rat hippocampus. Steady-state expression of C a V 1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of C a V 1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against C a V 1.2 and C a V 1.3 demonstrated the highest intensity of labeling in the proximal dendrites at all ages studied (P1–72). Immunohistochemical studies on one-week-old hippocampi demonstrated significantly more colocalization of GAB A B receptors with C a V 1.2 than with C a V 1.3, suggesting that modulation of L-type calcium current in early development is mediated through C a V 1.2 channels. 1. Introduction Calcium is an ideal signaling molecule within neurons because the intracellular concentration is kept very low by calcium binding proteins as well as transporters that sequester calcium in intracellular organelles. Therefore, very small changes in the intracellular calcium concentration can act as a molecular switch, controlling a variety of cellular processes such as regulation of gene expression, neurotransmitter release, propagation of action potentials, synaptic plasticity, neurite outgrowth, cell death, and muscle contraction. Increases in free intracellular calcium can be mediated through release from intracellular stores or by influx through ligand gated or voltage gated channels within the cell membrane. There are 5 broad classes of voltage dependent calcium channels (L, N, P/Q, R, T) characterized by their respective kinetics, voltage dependence, and pharmacological sensitivity (for review, see [1, 2]). The different physiological characteristics of these channels allow for diverse function. In addition to the biophysical properties of the channels, individual channels are located in different regions of neurons
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