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Brain synaptosomes display a diadenosine tetraphosphate (Ap 4 A)‐mediated Ca 2+ influx distinct from ATP‐mediated influx
Author(s) -
Pivorun E.B.,
Nordone A.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960601)44:5<478::aid-jnr8>3.0.co;2-c
Subject(s) - extracellular , depolarization , suramin , biophysics , dids , chemistry , verapamil , synaptosome , membrane potential , calcium , biochemistry , receptor , biology , membrane , organic chemistry
Studies undertaken to compare the effects of Ap 4 A and ATP on altering intrasynaptosomal Ca 2+ levels from deermouse brain reveal that both ligands induce a rapid influx of extracellular Ca 2+ . The Ca 2+ profile elicited by 167 μM Ap 4 A is “spike‐like” (half‐time for decline to baseline, 19.1 ± 1.2 sec), in contrast to the gradual decline observed with ATP (104.0 ± 7.4 sec). DIDS (4‐4′‐diisothiocyano‐2,2′‐disulfonic acid stilbene) and suramin preincubation alter only the ATP‐induced Ca 2+ profile. Cross‐desensitization studies indicate that prior application of ATP does not significantly affect the Ca 2+ influx elicited by Ap 4 A, and that prior application of Ap 4 A does not affect the Ca 2+ influx elicited by ATP. These results demonstrate that extracellular Ap 4 A and ATP elicit distinct intrasynaptosomal Ca 2+ influx profiles, and suggest that these two nucleotides may be interacting with distinct purinoceptor subclasses or purinoceptor‐effector complexes. Subjecting the synaptosomes simultaneously to depolarization and Ap 4 A, or to depolarization and ATP, induces an additive effect on Ca 2+ influx. Preincubation with verapamil negates the effects of depolarization without modifying the ligand‐elicited Ca 2+ fluxes. These results indicate the presence of Ap 4 A and ATP ligand‐gated channels that may function as modulators of neuronal activity. © 1996 Wiley‐Liss, Inc.