Levels of 1.2 L-Type Channels Peak in the First Two Weeks in Rat Hippocampus Whereas 1.3 Channels Steadily Increase through Development

Abstract

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 receptors. Of the four isoforms of L-type channels, only 1.2 and 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 1.2 and 1.3 in the CA1 region of rat hippocampus. Steady-state expression of 1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of 1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against 1.2 and 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 receptors with 1.2 than with 1.3, suggesting that modulation of L-type calcium current in early development is mediated through 1.2 channels.