Maturational change of KCl-induced Ca2+ increase in the rat brain synaptosomes

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 nh?). On the other hand, the time necessary for [Ca2+](i) to decrease to 50% of its maximal level (tau) 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 tau in adult rats were markedly reduced by verapamil, omega-agatoxin IVA, and omega-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 tau 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. (C) 1998 Published by Elsevier Science B.V. All rights reserved.