Characterization oc Ca2+-channels responsible for K+-evoked [H-3]noradrenaline release from rat brain cortex synaptosomes and their response to amyotrophic lateral sclerosis IgGs
C. Grassi et al., Characterization oc Ca2+-channels responsible for K+-evoked [H-3]noradrenaline release from rat brain cortex synaptosomes and their response to amyotrophic lateral sclerosis IgGs, EXP NEUROL, 159(2), 1999, pp. 520-527
The contribution of the different Ca2+-channel subtypes to the K+-evoked [H
-3]noradrenaline release from rat cerebral cortex synaptosomes has been inv
estigated. In the same experimental model, it was also verified whether the
calcium-mediated neurotransmitter release is influenced by IgGs purified f
rom sera of seven patients affected by sporadic amyotrophic lateral scleros
is. Synaptosome treatment with 3.0 mu M nifedipine or 2.0 mu M calciseptine
, which block L-type channels, slightly decreased [H-3]noradrenaline releas
e, the reduction being 7 and 13% of the control values, respectively. The b
lockade of N-type Ca2+-channels with omega-conotoxin-GVIA (0.001-1.0 mu M)
induced a concentration-dependent reduction of the neurotransmitter release
, with maximum effect of 34%. omega-Agatoxin-IVA failed to significantly af
fect the studied release, which was instead markedly reduced by omega-conot
oxin-MVIIC. After the blockade of N-type channels with maximal concentratio
ns of omega-conotoxin-GVIA, 3.0 mu M omega-conotoxin-MVIIC reduced the rele
ase by 58%. Synaptosome treatment with amyotrophic lateral sclerosis IgGs e
nhanced the K+-evoked [H-3]noradrenaline release, which was mostly mediated
by P/Q- and N-type Ca2+-channels. The increase induced by pathologic IgGs
(0.2 mg/ml) ranged from 11 to 62% for the different patients, and it was co
ncentration-dependent. The basal release was instead unaffected by IgG trea
tment. The results of the present study suggest that the K+-evoked [H-3]nor
adrenaline release from brain cortex synaptosomes is mainly mediated by act
ivation of P/Q- and N-type Ca2+-channels. Autoantibodies present in the ser
a of patients affected by sporadic amyotrophic lateral sclerosis may intera
ct with these channels by producing an increased calcium influx, with conse
quent enhancement of the neurotransmitter release. Preliminary results of t
he present study have been published in abstract form (Martire et al., 1997
, Pharmacol. Res. 35:9). (C) 1999 Academic Press.