This paper interested me, and I've attempted to summarise it below.


http://www.nencki.gov.pl/pdf/an/vol61/miguel.pdf

"Sphingolipid derivatives modulate intracellular Ca2+ in rat synaptosomes"
Begona G. Miguel et al
Acta Neurobiol. Exp. 2001 61: 113-117
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In the presence of external calcium, Sphingosylphosphorylcholine
[SPC - an N-deacylated derivative of sphingomyelin] caused a rapid, dose-
dependent increase in intrasynaptosomal calcium. The effect was mediated
through nimodipine-sensitive channels and not IP3 / ryanodine receptors.
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SPC is a potent mitogen for many cells; it can act through PKC
and it can mobilise intracellular calcium through IP3-dependent and
independent means.

50uM SPC produced a maximal increase in intrasynaptosomal
calcium fluorescence in Fura-loaded synaptosomes (from 215 to 285 nM).
With external calcium present, this was sustained for around 3 min, without
external calcium it was transient. This implies that SPC has a dual action:
increasing calcium entry from external medium and mobilisation from
intracellular stores (masked by influx from external).

Heparin (blocks IP3 receptors) failed to stop SPC-mediated increase
in calcium therefore SPC was not acting through IP3 receptor calcium
channels. Ryanodine also failed in this respect thus ryanodine receptors
are not involved.

In Ca2+-free medium, thapsigargin (a microsomal Ca2+-ATPase
inhibitor) increased intrasynaptosomal calcium to 510nM. SPC had no effect
on this, suggesting mobilisation is from ER rather than microsomes.

Nimodipine, an amphiphilic L-type calcium channel inhibitor, can
cross the membrane and it blocked SPC over a concentration range of 5 - 20uM.
In astrocytes cultured in calcium-free medium, nimodipine depleted
intracellular
stores, thus nimodipine might inhibit both of SPC's calcium-mobilising routes;
entry across the membrane and release from intrasynaptosomal stores.

An intracellular sphingolipid-gated channel has been proposed
by others, and the authors of this paper have previously described the effects
of sphingosine derivatives on calcium increases in liver nuclei by a similar
intracellular (sphingosine-sensitive) calcium channel.

"The present findings suggest a potential role for sphingolipids in the
control
of the brain functions through regulation of cytosolic Ca2+ levels."