Y. Tanaka et S. Ando, Age-related changes in the subtypes of voltage-dependent calcium channels in rat brain cortical synapses, NEUROSCI RE, 39(2), 2001, pp. 213-220
Age-related changes in the relative contribution of voltage-dependent calci
um channel (VDCC) subtypes to depolarization-induced Ca2+ influx and in the
density of VDCC subtypes in cortical synapses were investigated using syna
ptosomes and their membrane preparations from brain cortices of Wistar rats
. The relative contribution of VDCC subtypes to Ca2+ influx was determined
by measuring the inhibition of depolarization-induced Ca2+ influx with foul
VDCC subtype-specific peptide blockers. In adult rat synaptosomes. L-, N-,
P- and Q-type channels accounted for 24, 32, 27 and 12% of the total Ca2influx, respectively. Brain aging significantly reduced the relative contri
butions of N- and P-type channels and increased the contribution of the cha
nnels resistant to the four blockers used. The densities of VDCC subtypes.
determined by binding experiments using radiolabeled PN200 -110, omega -con
otoxin GVIA and omega -conotoxin IL MVIIC. were found to be significantly d
ecreased in aged synaptic plasma membranes. On the contrary. the dissociati
on constants of the blockers were not changed except for PN200-110-sensitiv
e L-type channels. These results suggest that aging alters the relative con
tributions of each VDCC subtype to depolarization-induced C2+ influx and de
creases the number of VDCCs in rat brain cortical synapses. These changes i
n VDCCs may lead to age-related hypofunction of synaptic neurotransmission
in brain cortices. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neur
oscience Society. All rights reserved.