ON THE MECHANISMS UNDERLYING HYPOXIA-INDUCED MEMBRANE DEPOLARIZATION IN STRIATAL NEURONS

Clinical and experimental evidence has shown that the striatal neurons are particularly vulnerable to hypoxia and ischaemia. An excessive ex citatory action of glutamate, released by the corticostriatal terminal s, has been implicated in this peculiar vulnerability of striatal neur ons. We have studied the effects of hypoxia on the membrane properties of striatal neurons intracellularly recorded from a corticostriatal s lice preparation. Brief (2-10 min) periods of hypoxia produced reversi ble membrane depolarizations. During the initial phase of the hypoxia- induced depolarization the frequency of action potential discharge was transiently increased; 2-3 min after the onset of hypoxia the firing activity was fully abolished. Brief periods of hypoxia also caused a r eversible reduction of the amplitude of the excitatory postsynaptic po tentials (EPSPs) evoked by cortical stimulation. Longer periods of hyp oxia (12-20 min) produced irreversible membrane depolarizations. In vo ltage-clamp experiments hypoxia caused an inward current coupled with an increased membrane conductance. Tetrodotoxin (TTX) or low calcium ( Ca2+)-high magnesium containing solutions blocked synaptic transmissio n, bur they did not reduce the hypoxia-induced electrical changes. Ant agonists of excitatory amino acid receptors failed to affect the elect rical effects caused by oxygen deprivation. Hypoxia-induced inward cur rents were reduced either by the potassium (K+) channel blockers, bari um and tetraethyl ammonium (TEA) cations, or by lowering external sodi um (Na+) concentration. Blockade of ATP-dependent Na+-K+ pump by both ouabain and strophanthidin enhanced hypoxia-induced membrane depolariz ation/inward current. Our findings indicate that the release of excita tory amino acids does not seem to be required for the acute hypoxia-in duced electrical changes in striatal neurons. Moreover TTX-resistant N a+ influx and K+ currents seem to play an important role in the genera tion of hypoxia-induced electrical changes. These data also suggest th at the selective vulnerability of striatal neurons to oxygen deprivati on may be caused by their peculiar sensitivity to energy metabolism fa ilure.