Abstract
To investigate maturational change in the susceptibility of voltage-dependent calcium
(Ca2+) channels (VDCC) in the brain to excessive depolarization, which is likely to occur
during hypoxia or ischemia, we studied depolarization-induced increases in Ca2+ concentration in cortical synaptosomes ([Ca2+]i) obtained from young (8, 15, 22, 36, and 43-day-old) and adult rats using fura 2-AM
as a Ca2+ indicator. The effects of Ca2+ antagonists on the increase were also studied. The maximal increase in [Ca2+]i caused by 50 mM KCl-induced depolarization was significantly lower in 8-day-old rats
(73.3 nM) compared with that in adult rats (133.6 nM). On the other hand, the time
necessary for [Ca2+]i to decrease to 50% of its maximal level (τ) was significantly shorter in immature rats compared with that in adult rats and
was particularly short in 8- and 15-day-old rats (0.28 and 0.40 min vs. 3.85 for adult
rats). The maximal increase in [Ca2+]i in 22-day-old rats and τ in adult rats were markedly reduced by verapamil, ω-agatoxin IVA, and ω-conotoxin GVIA (antagonists of L-, P-, and N-type Ca2+ channels, respectively) to similar extents, while a mixture of the three antagonists
markedly decreased both maximal increase and τ in 8- and 22-day-old and adult rats. These results indicate that depolarization-induced
Ca2+ influx through VDCCs in immature rat brain is less pronounced than that in adult
rats, and suggest that the susceptibility of all of L-, N-, and P-type Ca2+ channels is increased during maturation in the first few weeks after birth. This
lower susceptibility to depolarization might be involved in the resistance to hypoxia
in immature animals.
Keywords
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Article info
Publication history
Accepted:
April 2,
1998
Received in revised form:
February 12,
1998
Received:
November 27,
1997
Identification
Copyright
© 1998 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
