Stimulus-Mitosis Coupling in the Rat Thymic Lymphocyte

Abstract

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.

Date of Award	1981
Original language	English