MATURATIONAL CHANGE OF KCL-INDUCED CA2-BRAIN SYNAPTOSOMES( INCREASE IN THE RAT)

To investigate maturational change in the susceptibility of voltage-de pendent calcium (Ca2+) channels (VDCC) in the brain to excessive depol arization, which is likely to occur during hypoxia or ischemia, we stu died depolarization-induced increases in Ca2+ concentration in cortica l 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 effec ts of Ca2+ antagonists on the increase were also studied. The maximal increase in [Ca2+](i) caused by 50 mM KCl-induced depolarization was s ignificantly lower in 8-day-old rats (73.3 nM) compared with that in a dult 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 s horter in immature rats compared with that in adult rats and was parti cularly short in 8- and 15-day-old rats (0.28 and 0.40 min vs. 3.85 fo r adult rats). The maximal increase in [Ca2+](i) in 22-day-old rats an d 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 th ree antagonists markedly decreased both maximal increase and tau in 8- and 22-day-old and adult rats. These results indicate that depolariza tion-induced Ca2+ influx through VDCCs in immature rat brain is less p ronounced than that in adult rats, and suggest that the susceptibility of all of L-, N-, and P-type Ca2+ channels is increased during matura tion in the first few weeks after birth. This lower susceptibility to depolarization might be involved in the resistance to hypoxia in immat ure animals. (C) 1998 Published by Elsevier Science B.V. All rights re served.