Characterization of a novel intracellular sphingolipid-gated Ca(2+)-permeable channel from rat basophilic leukemia...

Sphingolipids stimulate the release of Ca2+ from intracellular stores. However, the mechanism by which this process occurs has not been characterized. Through single-channel recording from microsomes incorporated into planar lipid bilayers, we describe a novel channel that gates Ba2+ in response to sphingosylphosphorylcholine. The channel is both ligand-gated and voltage-modulated. Maximal open probability is observed between -10 and -20 mV and has a relatively high conductance (160 picosiemens with 53 mM Ba2+). We also observe that Ca2+ efflux from permeabilized rat basophilic leukemia cells is not antagonized by heparin, La3+, Ni2+, nifedipine, or omega-conotoxin GVIa. The sphingolipid-gated Ca(2+)-permeable channel is therefore a new member of the Ca(2+)-permeable, ligand-gated channel family.