Anti-Ig-induced calcium influx in rat B lymphocytes mediated by cGMP through a dihydropyridine-sensitive channel

Abstract

In contrast to excitable tissues where calcium channels are well characterized, the nature of the B lymphocyte calcium channel is unresolved. Here, we demonstrate by single cell analysis of freshly isolated rat B cells that the anti-immunoglobulin (Ig)-induced calcium influx takes place through a channel which shares pharmacologic and serologic properties with the L- type calcium channel found in excitable tissues. It is sensitive to the dihydropyridines nicardipine and Bay K 8644, to calciseptine, and to an anti- peptide antibody raised against the α1 subunit of the L-type calcium channel, but is voltage-insensitive. Anti-α1 and anti-α2 antibodies stain B but not T lymphocytes. Application of a cGMP agonist, measurement of cGMP levels in anti-Ig-stimulated B cells, and examining the effect of a guanylyl cyclase inhibitor on the anti-Ig response show that cGMP mediates the influx. This possibly involves a cGMP-dependent protein kinase. The anti-Ig-induced response is not abolished by prior treatment of B cells with a high dose of thapsigargin. These findings undermine the widely held belief of a categorical divide between excitable and non-excitable tissue calcium channels, demonstrate the limitations of the capacitative calcium influx theory, and point to a distinction between the calcium response mechanisms utilized by B and T lymphocytes.