Ca(2+)-activated K+ channels in human leukemic T cells.
Using the patch-clamp technique, we have identified two types of Ca(2+)-activated K+ (K(Ca)) channels in the human leukemic T cell line. Jurkat. Substances that elevate the intracellular Ca2+ concentration ([Ca2+]i), such as ionomycin or the mitogenic lectin phytohemagglutinin (PHA), as well as whole-cell dialysis with pipette solutions containing elevated [Ca2+]i, activate a voltage-independent K+ conductance. Unlike the voltage-gated (type n) K+ channels in these cells, the majority of K(Ca) channels are insensitive to block by charybdotoxin (CTX) or 4-aminopyridine (4-AP), but are highly sensitive to block by apamin (Kd less than 1 nM). Channel activity is strongly dependent on [Ca2+]i, suggesting that multiple Ca2+ binding sites may be involved in channel opening. The Ca2+ concentration at which half of the channels are activated is 400 nM. These channels show little voltage dependence over a potential range of -100 to 0 mV and have a unitary conductance of 4-7 pS in symmetrical 170 mM K+. In the presence of 10 nM apamin, a less prevalent type of K(Ca) channel with a unitary conductance of 40-60 pS can be observed. These larger-conductance channels are sensitive to block by CTX. Pharmacological blockade of K(Ca) channels and voltage-gated type n channels inhibits oscillatory Ca2+ signaling triggered by PHA. These results suggest that K(Ca) channels play a supporting role during T cell activation by sustaining dynamic patterns of Ca2+ signaling.
Department of Physiology and Biophysics, University of California, Irvine 92717.
S
S
Grissmer
R S
RS
Lewis
M D
MD
Cahalan
D015761:4-Aminopyridine / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D018999:Charybdotoxin; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D015458:Leukemia, T-Cell / Q000378:metabolism*; D010835:Phytohemagglutinins; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010835:Phytohemagglutinins; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D001030:Apamin; D015759:Ionomycin; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium