Ionic mechanisms of anoxia : potential role for y-aminobutyric acid.

Abstract

When ionic changes induced by GABA (5 mM) were compared to those evoked by O2 replacement by N2 for 5 min, anoxic responses were found to be very similar in direction of change and time-course. In stratum pyramidale (SP) there were increases in [K+] o and [Cl--]o and a decrease in [Na +]o, and in stratum radiatum (SR) an increase in [K +]o and decreases in [Cl--]o and [Na+]o. Changes in SR were greater than those in SP, except for D [K+]o evoked by GABA. To estimate changes in the extracellular space (ECS), variations in [TMA+] o were recorded during GABA and N2 exposures. Volume decreases were observed with both GABA and anoxia and significantly less in SP than in SR: 5.3 +/- 0.03% and 6.2 +/- 0.8%, respectively with N2 and 4.6 +/- 0.2% and 4.8 +/- 0.3% with GABA. The ECS reduction was insufficient to account for the ionic changes observed. The GABAA receptor antagonist, BMI (bicuculline methioidide) (100 m M) reversibly attenuated all ion changes evoked by GABA and N 2. In SP BMI depressed increases in [K+]o and [CI--]o with GABA by 90%, and with N 2 by 50--60%. In SR the D [K+]o evoked by GABA was blocked, and that with anoxia was attenuated by 70%; decreases in [Cl--] o were depressed by more than 50%, and [Na+]o changes in SP and SR were decreased by 20--30%. The GABAB agonist, baclofen (10° -- 3 x 10 3 m M) evoked dose-dependent increases in [K+]o in SP and SR, with EC50 = 40 and 39 m M, respectively. The sigmoid concentration-response curves and sensitivity of responses to the GABAB antagonists, indicate a receptor-mediated increase in D [K+]o, due to an increase in gK. The similar EC50 values at the soma and dendrites suggests that their GABAB receptors are identical. The higher affinity of GABA B cf. GABAA receptors supports the possibility that an early component of anoxic-evoked K+ accumulation may be due to activation of both GABAA and GABAB receptors. The observation that [K+]o increase with N2 can be enhanced by GABAB antagonism may reflect a protectant action of GABA B receptors by decrease of glutamate release from terminals and postsynaptic hyperpolarization. (Abstract shortened by UMI.)