Stimulus-Mitosis Coupling in the Rat Thymic Lymphocyte

Various extracellular stimuli provoke the entry of normally quiescent rat thymic lymphocytes into the cell division cycle. This study has investigated the events which follow signal presentation and which culminate in cell cycle entry. The initial experiments examined mitotic activity in cultured thymocytes exposed to mitogenic and antimitogenic compounds. Like stimuli for secretion and contraction in other tissues, mitogens show an intimate dependency upon the extracellular cationic environment for their activity. Subsequent work therefore investigated the redistribution of various cations across the plasma membrane initiated by mitogenic signals. Thirty minutes after an elevation of the extracellular calcium concentration, which is believed to be a primary mitogenic signal in vivo, cultured thymocytes were committed to divide. Stimulation was only evident when free access of ionized calcium to the cytosol was unimpeded. A three-fold increase in extracellular calcium increased intracellular calcium approximately one hundred-fold and was associated with heightened potassium exit. An enhanced potassium efflux has been observed in a variety of tissues consequent upon an elevation in the free cytosolic calcium concentration. Via this indicator, several hormonal and non-hormonal mitogens were found to increase ionized calcium in the thymocyte cytosol although they failed to promote calcium influx. Those mitogens which required an extracellular supply of either calcium or magnesium ions, all raised intracellular calcium concentrations. In the case of those mitogens which interfered primarily with sodium metabolism, this was achieved by an inhibition of calcium extrusion. Thus a rise in cytosolic ionised calcium, which is known to couple extracellular signals to metabolic events such as secretion and contraction in various tissues, now appears to play a key role in stimulus-mitosis coupling. The increased free calcium concentrations created by enhanced entry, impaired exit or mobilization of intracellular stores provides the link between extracellular mitogenic signals and the intracellular cell cycle regulatory mechanisms.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Aston University

Year dc:date.issued

1981

Author dc:creator

• Atkinson, Michael J.

DOI dc:identifier.doi

https://doi.org/10.48780/publications.aston.ac.uk.00010526

OAI identifier oai:identifier

oai:publications.aston.ac.uk:10526