HCO3(-) ions increase mast cell sensitivity to thapsigargin-induced Ca(2+) entry.
In rat mast cells Ca(2+) entry is modified by the presence or absence of other ions in the external medium. HCO3(-) ions, which modify mast cell degranulation, seemed to modulate the Ca(2+) entry elicited by the intracellular Ca(2+)-ATPase inhibitor thapsigargin. In this work we studied the regulation of the Ca(2+) entry by HCO3(-) and its relationship with exocytosis. The Ca(2+) entry was activated by thapsigargin and Ca(2+) in mast cells bathed by a HCO3(-)-buffered medium or a HCO3(-)-free medium. Both Ca(2+) entry and exocytosis were enhanced by the presence of HCO3(-) ions. Nondegranulated mast cells showed a low Ca(2+) entry either in the presence or absence of HCO3(-). Thus, mast cells with a high [Ca(2+)](i) increase in a HCO3(-)-buffered medium undergo degranulation. In the same cells a second Ca(2+) entry was significantly higher than the first Ca(2+) entry in a HCO3(-)-free medium, while in a HCO3(-)-buffered medium the first and second Ca(2+) entries reached similar [Ca(2+)](i) levels. Although the second Ca(2+) entry is high in a HCO3(-)-free medium, degranulation is still low. Our results demonstrate that HCO3(-) ions increase the capacitative Ca(2+) entry and the sensitivity of mast cells to intracellular Ca(2+) in order to induce degranulation.
Vilariño
N
N
Departamento de Farmacología, Universidad Santiago de Compostela, Lugo, 27002, Spain.
De la Rosa
L A
LA
Vieytes
M R
MR
Botana
L M
LM
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D016257:Fura-2; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology*
D001639:Bicarbonates; D002021:Buffers; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2