Sodium block and depolarization diminish P2Z-dependent Ca2+ entry in human B lymphocytes.
Despite a high Ca2+ -permeability of the P2Z receptor in human B lymphocytes, extracellular ATP4- has only a minor effect on global [Ca2+]i. The aim of this study was to reveal the mechanisms responsible for this discrepancy. We investigated the relationship between ATP4- -application, Cai 2+ -response, membrane current and membrane potential in two human B cell lines and in human tonsillar B cells. This was achieved by a combination of FACS- and voltage clamp measurements and the usage of appropriate voltage- and Ca2 -sensitive fluorescent dyes. ATP4 -induced changes in whole-cell current and [Ca2]i were blocked by extracellular as well as intracellular Na+. Under current clamp conditions, ATP4- -induced Na+ -entry diminished the Ca2+ entry via reduction of the driving force. A substantial increase in [Ca2+]iinduced by ATP4- was only observed in Na+ -free solutions. The pathway of signal transduction activated by ATP4via P2Z receptor of human B lymphocytes under physiological conditions seems not to operate by an increase in the global intracellular Ca2+ -concentration, but rather by the depolarization of the cell membrane as a result of the Na+-influx.
Löhn
M
M
Franz-Volhard-Klinik am Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
Klapperstück
M
M
Riemann
D
D
Markwardt
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D014066:Palatine Tonsil / Q000166:cytology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000819:agonists* / Q000378:metabolism / Q000494:pharmacology
C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium