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Reciprocal regulation of K+ channels by Ca2+ in intact human T lymphocytes. Recept Channels 1993;1(3):201-15

Date

01/01/1993

Pubmed ID

7922020

Scopus ID

2-s2.0-0027135847   18 Citations

Abstract

The requirement for increased [Ca2+]i during T cell activation is well established. In the present study, we have used the cell-attached configuration of the patch-clamp technique and Ca2+ spectrofluorometry to investigate the regulation of K+ channel activity by intracellular calcium [Ca2+]i in intact human T lymphocytes. The predominant ion current in resting human T cells is a voltage-dependent K+ current, K(V), which is susceptible to second-messenger regulation. We report here that K(V) channel activity is reversibly inhibited at all relevant membrane potentials by a rise in [Ca2+]i induced by Ca2+ ionophore or the mitogens, concanavalin A or phytohemagglutinin. Consistent with this Ca2+ dependence, lowering [Ca2+]i with Ca(2+)-depleted medium can induce K(V) channel activity in otherwise quiet patches. We have also found two Ca(2+)-activated K+ channels (K(Ca)), a 9 pS channel and an inwardly rectifying 11-25 pS channel, similar to those we found in rat thymic T cells and human B cells. The sensitivity of these K(Ca) channels to [Ca2+]i suggests reciprocal regulation with that of K(V) channels. A considerable lag between mitogen treatment and induction of 9 pS K(Ca) activity, the decrease in this channel's activity in the continued presence of high [Ca2+]i or upon patch excision, and the decreased sensitivity of K(V) to Ca2+i block in disrupted cells all argue for the involvement of intracellular factors. During [Ca2+]i-mediated inhibition of K(V) channels, the recruitment of distinct K(Ca) channels is likely to play a central role in maintaining cell hyperpolarization and a sustained driving force for Ca2+ influx during T-cell activation.

Author List

Schlichter LC, Pahapill PA, Schumacher PA

Author

Peter A. Pahapill MD, PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Action Potentials
Calcium
Concanavalin A
Electric Conductivity
Humans
In Vitro Techniques
Intracellular Fluid
Ionomycin
Membrane Potentials
Phytohemagglutinins
Potassium Channels
T-Lymphocytes