Characterization of a novel intracellular sphingolipid-gated Ca²⁺-permeable channel from rat basophilic leukemia cells

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 ω-conotoxin GVIa. The sphingolipid-gated Ca²⁺-permeable channel is therefore a new member of the Ca²⁺-permeable, ligand-gated channel family.