Ca(2+)-activated K+ channels in human leukemic T cells

J Gen Physiol. 1992 Jan;99(1):63-84. doi: 10.1085/jgp.99.1.63.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Apamin / pharmacology
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Charybdotoxin
  • Humans
  • Ionomycin / pharmacology
  • Leukemia, T-Cell / metabolism*
  • Phytohemagglutinins
  • Potassium / metabolism*
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Scorpion Venoms / pharmacology
  • Tumor Cells, Cultured

Substances

  • Phytohemagglutinins
  • Potassium Channels
  • Scorpion Venoms
  • Charybdotoxin
  • Apamin
  • Ionomycin
  • 4-Aminopyridine
  • Potassium
  • Calcium