HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lai, Z.-F. Articles by Nishi, K. Search for Related Content PubMed PubMed Citation Articles by Lai, Z.-F. Articles by Nishi, K.

An Amiloride-Sensitive and Voltage-Dependent Na⁺ Channel in an HLA-DR-Restricted Human T Cell Clone¹

Zhong-Fang Lai^2,3,*, Yu-Zhen Chen^3,, Yasuharu Nishimura and Katsuhide Nishi^*

^* Department of Pharmacology, Kumamoto University School of Medicine, and Division of Immunogenetics, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan

We investigated changes in voltage-gated Na⁺ currents and effects of extracellular Na⁺ on proliferation in HLA-DR-restricted human CD4⁺ ß T cells after stimulation with a non-self antigenic peptide, M12p54–68. In the absence of antigenic peptide, neither single (n = 80) nor APC-contacted (n = 71) T cells showed voltage-gated inward currents recording with whole-cell patch-clamp techniques, even with Ca²⁺ and Na⁺ ions present in the perfusion solution. However, with the same recording conditions, 31% (26 of 84) of APC-contacted T cells stimulated with the antigenic peptide showed voltage-dependent inward currents that were elicited from -60 mV. The inward currents were not inhibited in extracellular Ca²⁺-free conditions or in the presence of 1 mM NiCl₂. However, they were completely inhibited in extracellular Na⁺-free conditions, which were made by replacing Na⁺ with iso-osmotic N-methyl-D-glucamine or choline. The Na⁺ currents were insensitive to tetrodotoxin, a classical blocker of Na⁺ channels, but were dose-dependently inhibited by amiloride, a potassium-sparing pyrazine diuretic. Furthermore, the Ag-specific proliferative response of T cells was completely inhibited in Na⁺-free Tyrode’s solution and was suppressed by amiloride in a dose-dependent manner. Our findings suggest that activation of amiloride-sensitive and voltage-gated Na⁺ channels would be an important step to allow an adequate influx of Na⁺ and maintain a sustained high Ca²⁺ level during T cell activation.

This article has been cited by other articles:

				Z.-F. Lai, Y.-Z. Chen, L.-P. Feng, X.-M. Meng, J.-F. Ding, L.-Y. Wang, J. Ye, P. Li, X.-S. Cheng, Y. Kitamoto, et al. Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H708 - H716. [Abstract] [Full Text] [PDF]

				R. G. Fernandez, J. A. Leehan, R. F. Pastrana, and R. O. Muniz Effect of Malnutrition on K+ Current in T Lymphocytes Clin. Vaccine Immunol., July 1, 2005; 12(7): 808 - 813. [Abstract] [Full Text] [PDF]

				D. A. Bechtold, X. Yue, R. M. Evans, M. Davies, N. A. Gregson, and K. J. Smith Axonal protection in experimental autoimmune neuritis by the sodium channel blocking agent flecainide Brain, January 1, 2005; 128(1): 18 - 28. [Abstract] [Full Text] [PDF]

				P. Bradding, Y. Okayama, N. Kambe, and H. Saito Ion channel gene expression in human lung, skin, and cord blood-derived mast cells J. Leukoc. Biol., May 1, 2003; 73(5): 614 - 620. [Abstract] [Full Text] [PDF]