Response to fibronectin-integrin interaction in leukaemia cells: delayed enhancing of a K+ current.
In murine erythroleukaemia cells, the response of ion channels was followed before and after contact with fibronectin-coated latex microspheres. Patch-clamp experiments in 'whole-cell' and in 'cell-attached' configurations showed that cell adhesion to fibronectin promoted plasma membrane hyperpolarization mediated by activation of potassium channels that were indistinguishable from calcium-dependent potassium channels K(Ca) in these cells. K+ current increase began in 5-6 min and was completed about 10 min after the first contact. The timecourse of this process recorded from 'whole-cell' was very similar to that followed in intact cells by observing the increase of single channel currents. The open probability of single channels in the patch increased after contact, revealing that this activation is propagated at distance from the adhesion site. The slow onset of the effect suggests the presence of a complex regulatory pathway between fibronectin-integrin binding and activation of potassium channels. Decreasing cytoplasmic free Ca2+ concentration to pCa 9 diminished, but did not inhibit, the response. The current induced by fibronectin was not blocked by apamin, alpha-charybdotoxin or glibenclamide, but was abolished by high concentrations of tetraethylammonium (TEA). These data suggest for the first time the existence of a specific regulative connection between integrin receptors and ionic channels.
Department of General Physiology and Biochemistry, University of Milan, Milano, Italy.
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A
Becchetti
A
A
Arcangeli
M R
MR
Del Bene
M
M
Olivotto
E
E
Wanke
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D005353:Fibronectins; D016023:Integrins; D015221:Potassium Channels