Ontogeny of voltage-sensitive calcium channel alpha(1A) and alpha(1E) subunit expression and synaptic function in rat central nervous system.
Immunohistochemical expression in the neocortex, hippocampus and cerebellum of the alpha(1A) or alpha(1E) subunit of the voltage-sensitive Ca(2+) channel was examined in Long-Evans hooded rats on gestational day 18 and postnatal days 1, 4, 7, 10, 14, 21, 90, 360 and 720. On gestational day 18 and postnatal day 1, alpha(1A) immunoreactivity was more dense in the neocortex and hippocampus than the cerebellum. By postnatal day 7, levels of alpha(1A) immunoreactivity increased dramatically in the cerebellum, while in neocortex, alpha(1A) immunoreactivity became more sparse, which approached the more diffuse pattern of cellular staining in the mature brain. Expression of alpha(1E) in the neocortex, hippocampus and cerebellum was much less dense than alpha(1A) between gestational day 18 and postnatal day 4. There was also significant alpha(1E) immunoreactivity in the mossy fibers of the hippocampus and in dendrites of Purkinje cells of the cerebellum. Depolarization-dependent 45Ca(2+) influx was examined in rat brain synaptosomes on postnatal days 4, 7, 10, 14, 21 and >60. In neocortical and hippocampal synaptosomes, 45Ca(2+) influx increased steadily with age and reached adult levels by postnatal day 10. In cerebellar synaptosomes, 45Ca(2+) influx was constant across all ages, except for a spike in activity which was observed on postnatal day 21. In neocortical and hippocampal synaptosomes, 100 nM omega-conotoxin MVIIC significantly inhibited 45Ca(2+) influx on postnatal day 10 and 14, respectively, or after. In cerebellar synaptosomes, influx was inhibited by omega-conotoxin MVIIC only on postnatal day 10 or prior. On postnatal day 7, 45Ca(2+) influx was not inhibited in neocortical and hippocampal synaptosomes by a combination of 10 microM nifedipine, 1 microM omega-conotoxin GVIA and 1 microM omega-conotoxin MVIIC, suggesting that an 'insensitive' flux predominates at this age. Overall, the results suggest that expression of voltage-sensitive Ca(2+) channels during development is dynamic and is important in central nervous system development.
Meacham
Connie A
CA
Neurotoxicology Division, MD-BIO5-5, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
White
Lori D
LD
Barone
Stanley
S
Shafer
Timothy J
TJ
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000502:physiology; D020908:Calcium Channels, R-Type / Q000187:drug effects / Q000502:physiology; D004622:Embryo, Mammalian; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D021122:Protein Subunits; D051381:Rats; D020318:Rats, Long-Evans; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020908:Calcium Channels, R-Type; D021122:Protein Subunits; D020960:omega-Conotoxins; D002118:Calcium