Intracellular calcium handling in rat olfactory ensheathing cells and its role in axonal regeneration.

Intracellular calcium handling by rat olfactory ensheathing cells (OECs) is implicated in their support for regrowth of adult CNS neurites in a coculture model of axonal regeneration. Pretreatment of OECs with BAPTA-AM to sequester glial intracellular calcium ([Ca(2+)](i)) reduces significantly the numbers of cocultured neurons regrowing neurites. The mean resting [Ca(2+)](i) of OECs cultured alone or with neurons was 300 nM in an external solution containing 2.5 mM calcium ([Ca(2+)](o)). In high [K(+)](o) or zero [Ca(2+)](o), resting [Ca(2+)](i) significantly decreased. [Ca(2+)](i) significantly increased when [Ca(2+)](o) was increased to 20 mM, lonomycin, thapsigargin, and thimerosal increased [Ca(2+)](i), and caffeine, ryanodine, and cyclopiazonic acid were without effect. Of the receptor agonists tested, none induced a change in [Ca(2+)](i). The calcium influx induced by high [Ca(2+)](o) was blocked by La(3+) and SKF96365, partially inhibited by Cd(2+), and insensitive to Ni(2+) and nifedipine. Pretreatment of OECs with La(3+) reduced neurite regrowth in cocultures in a concentration-dependent manner over the range that blocked the non-voltage-gated calcium flux through a putative TRP-like channel, which, we propose, is activated in OEC-mediated axonal regeneration.