hSK4/hIK1, a calmodulin-binding K(Ca) channel in human T lymphocytes. Roles in proliferation and volume regulation

Rajesh Khanna, Martin C. Change, William J. Joiner, Leonard K. Kaczmarek, Lyanne C. Schlichter

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Abstract

Human T lymphocytes express a Ca2+-activated K+ current (IK), whose roles and regulation are poorly understood. We amplified hSK4 cDNA from human T lymphoblasts, and we showed that its biophysical and pharmacological properties when stably expressed in Chinese hamster ovary cells were essentially identical to the native IK current. In activated lymphoblasts, hSK4 mRNA increased 14.6-fold (Kv1.3 mRNA increased 1.3-fold), with functional consequences. Proliferation was inhibited when Kv1.3 and IK were blocked in naive T cells, but IK block alone inhibited re-stimulated lymphoblasts. IK and Kv1.3 were involved in volume regulation, but IK was more important, particularly in lymphoblasts. hSK4 lacks known Ca2+- binding sites; however, we mapped a Ca2+-dependent calmodulin (CaM)- binding site to the proximal C terminus (Ct1) of hSK4. Full-length hSK4 produced a highly negative membrane potential (V(m)) in Chinese hamster ovary cells, whereas the channels did not function when either Ct1 or the distal C terminus was deleted (V(m) ~0 mV). Native IK (but not expressed hSK4) current was inhibited by CaM and CaM kinase antagonists at physiological V(m) values, suggesting modulation by an accessory molecule in native cells. Our results provide evidence for increased roles for IK/hSK4 in activated T cell functions; thus hSK4 may be a promising therapeutic target for disorders involving the secondary immune response.

Original languageEnglish (US)
Pages (from-to)14838-14849
Number of pages12
JournalJournal of Biological Chemistry
Volume274
Issue number21
DOIs
StatePublished - May 21 1999
Externally publishedYes

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T-cells
Calmodulin
Cricetulus
T-Lymphocytes
Ovary
Binding Sites
Cells
Calcium-Calmodulin-Dependent Protein Kinases
Messenger RNA
Accessories
Membrane Potentials
Complementary DNA
Modulation
Pharmacology
Membranes
Molecules
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

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hSK4/hIK1, a calmodulin-binding K(Ca) channel in human T lymphocytes. Roles in proliferation and volume regulation. / Khanna, Rajesh; Change, Martin C.; Joiner, William J.; Kaczmarek, Leonard K.; Schlichter, Lyanne C.

In: Journal of Biological Chemistry, Vol. 274, No. 21, 21.05.1999, p. 14838-14849.

Research output: Contribution to journalArticle

Khanna, Rajesh ; Change, Martin C. ; Joiner, William J. ; Kaczmarek, Leonard K. ; Schlichter, Lyanne C. / hSK4/hIK1, a calmodulin-binding K(Ca) channel in human T lymphocytes. Roles in proliferation and volume regulation. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 21. pp. 14838-14849.
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