A charybdotoxin-insensitive conductance in human T lymphocytes: T cell membrane potential is set by distinct K+ channels.

1. Changes in the membrane potential (Vm) of human T lymphocytes upon K+ channel block were inferred from alterations in K+ current reversal potential in cell-attached patches. It was found that a high concentration of charybdotoxin (100 nM, CTX), which blocks both voltage-gated (K(V)) and Ca(2+)-activated (K(Ca)) potassium channels in these cells, depolarizes Vm of lymphocytes only partially. Subsequent whole-cell measurements of the same cells showed that 39 +/- 25% of the voltage-gated current remains in the presence of CTX. 2. The CTX-resistant current reverses at potentials between -80 and -90 mV, indicating that it is K+ selective. The current is activated at more depolarized potentials compared with the unblocked IK(V) current with a threshold between -40 and -20 mV and a half-maximal activation at +50 mV. Inactivation during prolonged depolarization is slow. Steady-state inactivation is half-maximal at -45 mV and complete at potentials > -20 mV. The CTX-resistant IK(V) is completely blocked by nifedipine and is not sensitive to dendrotoxin. 3. The effect of nifedipine on the Vm of lymphocytes varies between cells depending on the contribution of the nifedipine-sensitive current to whole-cell IK(V). Combined application of CTX and nifedipine completely depolarizes Vm. 4. The extent to which T cell receptor-evoked Ca2+ signals of resting cells are inhibited by K+ channel blockers correlates with the magnitude of the depolarization induced by the drugs. Complete suppression of the response is achieved only by combined block of the CTX-sensitive and -insensitive IK(V). The enhanced Ca2+ response of activated cells, which express increased numbers of K(Ca) channels, is in addition subject to modulation by blockers which prevent the hyperpolarization during the Ca2+ rise mediated by these channels.