Activation of Ca2+ current in Jurkat T cells following the depletion of Ca2+ stores by microsomal Ca2+-ATPase inhibitors

B. A. Premack, T. V. McDonald, P. Gardner

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

The mechanism of TCR-stimulated Ca2+ influx was studied in the Jurkat human T cell line using Ca2+ indicator dyes and whole-cell patch clamp. Ca2+ influx induced by inositol 1,4,5-triphosphate (IP3)-coupled surface receptors (either the TCR or a heterologous muscarinic receptor) was compared with Ca2+ influx induced by inhibitors of the microsomal Ca2+-ATPase (thapsigargin, cyclopiazonic acid, di-tert-butylhydroquinone), which release stored Ca2+ without production of IP3. The same Ca2+ influx pathway could be activated by IP3-dependent or IP3-independent means, and therefore appeared to be regulated by the fullness of the microsomal Ca2+ stores rather than by the direct action of IP3. Depletion of stored Ca2+ by either receptor stimulation or microsomal Ca2+-ATPase inhibition activated a low conductance, Ca2+-selective, non-voltage-activated membrane current. Ca2+ currents induced by receptor stimulation and Ca2+-ATPase inhibition were not additive. Several properties of the depletion-activated Ca2+ current suggest that it is carried by a novel type of Ca2+ channel rather than an electrogenic carrier or pump. The conductance saturated when external Ca2+ was raised (K(d) ≃ 2 mM) and became highly permeable to monovalent cations when external Ca2+ was lowered to below 100 nM, much as has been observed for some voltage-gated Ca2+ channels. The Ca2+ current was reversibly blocked by >90% with 0.3 mM Cd2+, whereas the same concentration of Ni2+ or Co2+ blocked only 50 to 60% of the current. However, the absence of voltage-dependent activation, relative conductance sequence for divalent cations (Ca2+>Ba2+≃Sr2+>>Mn2+), and lack of inhibition by nifedipine, D600, diltiazem, δ-conotoxin, or aga-IVa were unlike that of voltage-gated Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)5226-5240
Number of pages15
JournalJournal of Immunology
Volume152
Issue number11
StatePublished - 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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