T-lymphocyte invasiveness: control by voltage-gated Na+ channel activity.
Whole-cell patch-clamp recordings showed that a sub-population (10%) of Jurkat cells, a model of human T-cells, expressed a functional voltage-gated sodium channel, which was tetrodotoxin (TTX)-resistant. Expression of voltage-gated sodium channel protein was confirmed by western blots. Semi-quantitative PCR analysis revealed that mRNAs for the alpha-subunits of multiple voltage-gated sodium channel subtypes were present but indicated that Na(v)1.5 was the predominant subtype, consistent with the TTX-resistant nature of the recorded currents. Importantly, 10 microM TTX reduced the number of Jurkat cells invading a Matrigel basement membrane by 93.0+/-5.5%. Since similar sodium channels have also been detected in normal human T-lymphocytes, it is concluded that the activity of voltage-gated sodium channels could represent a novel mechanism potentiating the invasive capacity of these cells.
Fraser
Scott P
SP
Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. s.p.fraser@iperial.ac.uk
Diss
James K J
JK
Lloyd
Louise J
LJ
Pani
Filippo
F
Chioni
Athina-Myrto
AM
George
Andrew J T
AJ
Djamgoz
Mustafa B A
MB
D006801:Humans; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015222:Sodium Channels; D013779:Tetrodotoxin