Blunted IgE-Mediated Activation of Mast Cells in Mice Lacking the Ca super(2+)-Activated K super(+) Channel K sub(Ca)3.1

• Published in: The Journal of immunology (1950) Vol. 180; no. 12; pp. 8040 - 8047
• Main Authors: Shumilina, Ekaterina, Lam, Rebecca S, Woelbing, Florian, Matzner, Nicole, Zemtsova, Irina M, Sobiesiak, Malgorzata, Mahmud, Hasan, Sausbier, Ulrike, Biedermann, Tilo, Ruth, Peter, Sausbier, Matthias, Lang, Florian
• Format: Journal Article
• Language: English
• Published: 01-06-2008
• ISSN: 0022-1767; 1550-6606

Mast cell stimulation by Ag is followed by the opening of Ca super(2+)-activated K super(+) channels, which participate in the orchestration of mast cell degranulation. The present study has been performed to explore the involvement of the Ca super(2+)-activated K super(+) channel K sub(Ca)3.1 in mast cell function. To this end mast cells have been isolated and cultured from the bone marrow (bone marrow-derived mast cells (BMMCs)) of K sub(Ca)3.1 knockout mice (K sub(Ca)3.1 super(-/-)) and their wild-type littermates (K sub(Ca)3.1 super(+/+)). Mast cell number as well as in vitro BMMC growth and CD117, CD34, and Fc epsilon RI expression were similar in both genotypes, but regulatory cell volume decrease was impaired in K sub(Ca)3.1 super(-/-) BMMCs. Treatment of the cells with Ag, endothelin-1, or the Ca super(2+) ionophore ionomycin was followed by stimulation of Ca super(2+)-activated K super(+) channels and cell membrane hyperpolarization in K sub(Ca)3.1 super(+/+), but not in K sub(Ca)3.1 super(-/-) BMMCs. Upon Ag stimulation, Ca super(2+) entry but not Ca super(2+) release from intracellular stores was markedly impaired in K sub(Ca)3.1 super(-/-) BMMCs. Similarly, Ca super(2+) entry upon endothelin-1 stimulation was significantly reduced in K sub(Ca)3.1 super(-/-) cells. Ag-induced release of beta -hexosaminidase, an indicator of mast cell degranulation, was significantly smaller in K sub(Ca)3.1 super(-/-) BMMCs compared with K sub(Ca)3.1 super(+/+) BMMCs. Moreover, histamine release upon stimulation of BMMCs with endothelin-1 was reduced in K sub(Ca)3.1 super(-/-) cells. The in vivo Ag-induced decline in body temperature revealed that IgE-dependent anaphylaxis was again significantly (by similar to 50%) blunted in K sub(Ca)3.1 super(-/-) mice. In conclusion, K sub(Ca)3.1 is required for Ca super(2+)-activated K super(+) channel activity and Ca super(2+)-dependent processes such as endothelin-1- or Ag-induced degranulation of mast cells, and may thus play a critical role in anaphylactic reactions.