Intracellular Ca2+ oscillations and membrane potential fluctuations in intact human T lymphocytes: role of K+ channels in Ca2+ signaling.
In intact human T lymphocytes, voltage-gated K+ [K(V)] channels and Ca(2+)-activated K+ [K(Ca)] channels have been recorded using the patch clamp technique in the cell-attached configuration. The reversal potential of the voltage-gated current with high K+ solution in the pipette gives a measure for the cell membrane potential (VM). The open probability of the K(Ca) channels gives a measure for intracellular Ca2+ concentration ([Ca2+]i). By simultaneous recording of both types of K+ channels, the interaction of VM and [Ca2+]i in T lymphocytes was investigated. It was demonstrated that VM fluctuates under resting conditions in a 20 mV range around an average value of -60 mV. In response to T cell receptor stimulation by PHA, rises in [Ca2+]i occur, which vary between cells from transient or sustained elevations to Ca2+ oscillations, in parallel with amplification of the hyperpolarizing deflections of VM. The correlation between VM and [Ca2+]i suggests that Ca2+ oscillations are modulated by positive feedback between Ca2+ influx, [Ca2+]i and VM mediated by K(Ca) channels and by intrinsic VM fluctuations caused by negative feedback between VM and the K(V) channel. Differences in the ratio between K(Ca) and K(V) channel numbers can account for the variability in Ca2+ responses between cells. The results predict periodic K(V) channel activity at rest and alternating K(V) and K(Ca) channel activity during Ca2+ signaling, which was consistent with subsequent observations.
Verheugen
J A
JA
Research Institute of Toxicology, Utrecht University, The Netherlands.
Vijverberg
H P
HP
D002118:Calcium / Q000378:metabolism*; D005246:Feedback; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D008213:Lymphocyte Activation; D018448:Models, Immunological; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D015221:Potassium Channels; D002118:Calcium