Involvement of intracellular regulatory systems in the adaptive effects of transient anoxia in vitro

Abstract

The involvement of the calcium and phosphoinositide intracellular regulatory systems in the molecular-cellular mechanisms of adaptation of the brain to hypoxia induced by transient anoxia were studied in slices of rat olfactory cortex. Anoxia lasting 2 min initiated the development of moderate but stable activation of intracellular regulatory systems during the reoxygenation period, with increases in binding of Ca2+ to intracellular hydrophobic domains and increases in the level of polyphosphoinositide metabolism. During this period, cells in the slices released neuromediator factors into the perfusion fluid; transfer of these to recipient slices induced similar changes in the activities of intracellular regulatory system components in the recipient slices. After anoxia lasting 10 min, NMDA-mediated pathogenic hyperactivity of the calcium and phosphoinositide systems developed. Preliminary moderate activation of these systems by transient anoxia or neuromodulator factors released by cells in response to transient anoxia prevented disruption of intracellular regulatory system activity induced by subsequent longer-lasting anoxia.

Calcium Transients in the Model of Rapidly Induced Anoxic Tolerance in Rat Cortical Slices: Involvement of NMDA Receptors

“…In particular, we previously noticed that, in olfactory cortical slices, in vitro 2-min PA improves the recovery of evoked focal potentials and prevents an excessive increase in Ca b induced by 10-min TA [15,18]. Similar results concerning neuronal activity and dynamics of Ca b in cat brain cortex were also obtained in vivo [12,30].…”

“…Still, the former phenomenon might play a signalling role for the induction of long-lasting tolerance. There is evidence that the mechanism of rapid preconditioning is associated with increased excitability of neurons [10][11][12], activation of A1 adenosine receptors [13], moderate increase in intracellular free and bound Ca 2+ levels and activation of phosphoinositide hydrolysis [14,15], and activation of protein kinase C [16,17], to mention only some examples of signal-related rapid responses to short-term anoxia. Nevertheless, the data accumulated so far are incomplete and no postulation of any unitary mechanism of rapid anoxic preconditioning can yet be made.…”

“…The anoxia-induced dynamics of calcium transients was shown in the model of TA. Moreover, it was found that activation of NMDA receptors mediates a strong increase in intracellular bound calcium levels, which may be significantly suppressed in slices treated with PA 90 min earlier [15,19].…”

Current insights into the molecular mechanisms of hypoxic pre- and postconditioning using hypobaric hypoxia

“…The second phase of hypoxic preconditioning, the phase of induction of long-term hypoxic tolerance, involves significant alterations of the intracellular signal transduction processes, primarily modest activation of the glutamatergic, calcium, phosphoinositide, cyclic AMP regulatory systems (Semenov et al, 2000 , 2002 ; Samoilov et al, 2003 ) and rapid changes in pro- and antioxidant reactions (Ravati et al, 2000 : Furuichi et al, 2005 ). This is followed by fast protein kinase- and protease-dependent modifications of ion channels, receptors, redox-sensitive proteins, as well as triggering of the third phase—the phase of expression of hypoxic tolerance.…”