Anti-Ig-induced calcium influx in rat B lymphocytes mediated by cGMP through a dihydropyridine-sensitive channel.
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 alpha1 subunit of the L-type calcium channel, but is voltage-insensitive. Anti-alpha1 and anti-alpha2 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.
Sadighi Akha
A A
AA
Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Willmott
N J
NJ
Brickley
K
K
Dolphin
A C
AC
Galione
A
A
Hunt
S V
SV
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D007072:Immunoglobulin D / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats
D000906:Antibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004546:Elapid Venoms; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D015124:8-Bromo Cyclic Adenosine Monophosphate; C067971:calciseptine; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium