Sodium-dependent, calmodulin-dependent transmitter release from synaptosomes

Effect of Pressure on the Release of Radioactive Glycine and γ‐Aminobutyric Acid from Spinal Cord Synaptosomes

“…Calcium-independent release accounted for 50% of [3H]glycine efflux and up to 75% for [3H]GABA efflux. Similar findings for calcium-independent release have been reported for glycine, GABA, and dopamine in brain slices, spinal cord slices, retinal tissue, and brain synaptosomes (Moscowitz and Cutler, 1980;Cunningham and Neal, 1981;Sandoval et al, 1985;Arias and Tapia, 1986;Okuma and Osumi, 1986;Jonsson et al, 1986). The calcium-independent release appears to be associated with the particular transmitter type, since acetylcholine and norepinephrine are reported to be highly calcium dependent and the release of these compounds is essentially inhibited when calcium is absent (Blaustein et al, 1972;Cunningham and Neal, 198 1 ;Arias and Tapia, 1986;Okuma and Osumi, 1986).…”

“…Hammerstad et al ( 197 1) made a similar observation when they showed that glycine and GABA were highly calcium dependent when electrically evoked from rat spinal cord slices. However, glycine, GABA, and dopamine all show calcium independence when stimulated with high K+ (i.e., >30 mM K+), veratridine, ouabain, quinidine, or monensin (Sandoval, 1980;Cunningham and Neal, 1981;Sandoval et al, 1985). The mechanism of the calcium-independent release is currently unclear.…”

“…The reversal of a bidirectional sodium-dependent membranebound camer for glycine or GABA, or the mobilization of cytosolic calcium from intraterminal stores cannot adequately explain this phenomenon (Moscowitz and Cutler, 1980;Sihra et al, 1984;Arias and Tapia, 1986). There is evidence, though, that intraterminal sodium content is an important factor contributing to the calcium-independent release (Minchin, 1980;Cunningham and Neal, 198 I ;Sihra et al, 1984;Sandoval et al, 1985;Arias and Tapia, 1986).…”

Novel interactions of cations with dihydropyridine calcium antagonist binding sites in brain

“…The high affinity binding site for Ca2" may represent a calcium binding protein such as calmodulin. Calmodulin, present in large quantities in the brain (Wallace et al, 1978;Sandoval et al, 1985) is activated fully by calcium concentrations in the range of 10-6-10-4M. The finding that Mg2' and Mn2" did not possess a high affinity interaction site agrees well with their inability to activate fully calmodulin (Chao et al, 1984), further stsggesting the association of a calcium binding protein with the high affinity Ca2" binding site.…”

“…Modulation of the DHPCA binding site by Na' may underlie facilitation ofthe inhibitory activity ofDHPCAs on the rapid phase ofcalcium uptake into synaptosomes by removal of extra-synaptic Na' (Turner & Goldin, 1985). Monovalent cation activity at the DHPCA binding site may also be linked to modulation of intrasynaptic terminal levels of Na' and perhaps K+, changes in intrasynaptic terminal levels ofNa+ playing an important role in neurotransmitter release (Sandoval et al, 1985). Although highly speculatory, the implication of such a non-calcium channel function for DHPCA binding sites in neuronal tissue would seem appropriate, given (1) the lack of a potent calcium current blocking activity for DHPCAs in neuronal tissue, and (2) the effect of the DHP calcium agonist Bay K 8644 (Schramm et al, 1983;Janis et al, 1984) at enhancing neurotransmitter release and depolarization-dependent phosphoinositol turnover in rat brain slices (Middlemiss & Spedding, 1985;Kendall & Nahorski, 1985) in an apparently Ca2+-independent (Rampe et al, 1985), but DHPCA-sensitive manner (Middlemiss & Spedding, 1985).…”