A CHARYBDOTOXIN-INSENSITIVE CONDUCTANCE IN HUMAN T-LYMPHOCYTES - T-CELL MEMBRANE POTENTIAL IS SET BY DISTINCT K+ CHANNELS

1. Changes in the membrane potential (V-m) of human T lymphocytes upon K+ channel block were inferred from alterations in K+ current reversa l potential in cell-attached patches. It was found that a high concent ration of charybdotoxin (100 nM, CTX), which blocks both voltage-gated (K(V)) and Ca2+-activated (K(Ca)) potassium channels in these cells, depolarizes V-m of lymphocytes only partially. Subsequent whole-cell m easurements of the same cells showed that 39 +/- 25% of the voltage-ga ted current remains in the presence of CTX. 2. The CTX-resistant curre nt reverses at potentials between -80 and -90 mV, indicating that it i s K+ selective. The current is activated at more depolarized potential s compared with the unblocked I-K(V) current with a threshold between -40 and -20 mV and a half-maximal activation at +50 mV. Inactivation d uring prolonged depolarization is slow. Steady-state inactivation is h alf-maximal at -45 mV and complete at potentials > -20 mV. The CTX-res istant I-K(V) is completely blocked by nifedipine and is not sensitive to dendrotoxin. 3. The effect of nifedipine on the V-m of lymphocytes varies between cells depending on the contribution of the nifedipine- sensitive current to whole-cell I-K(V). Combined application of CTX an d nifedipine completely depolarizes V-m. 4. The extent to which T cell receptor-evoked Ca2+ signals of resting cells are inhibited by K+ cha nnel blockers correlates with the magnitude of the depolarization indu ced by the CTX-sensitive and -insensitive I-K(V). The enhanced Ca2+ re sponse of activated cells, which express increased numbers of K(Ca) ch annels, is in addition subject to modulation by blockers which prevent the hyperpolarization during the Ca2+ rise mediated by these channels .