Abstracts

In humans who suffer seizures, a common technique to accentuate EEG abnormalities is hyperventilation, which produces alkalosis. We sought to elucidate potential underlying mechanisms for this effect by studying the effects of alkalosis in hippocampal area CA3 in brain slices. This preparation has been used extensively to study pathological epileptiform activity. 400uM slices were prepared from male Sprague Dawley rats, aged 4-8 weeks using a McIlwain tissue chopper. Slices were cut and stored in ACSF.
SPONTANEOUS POPULATION BURSTING: Extracellular field recordings were obtained from CA3 pyramidal cell layer. Bursting was induced by either single tetanic stimulation (100 Hz x 1 sec) in modified ACSF (in mM): 3.3 K⁺, 0.9 Mg²⁺, 1.5 Ca²⁺) or PTX (100uM) + CGP (1uM) to block GABA[sub]A[/sub] and GABA[sub]B [/sub]receptors. Changes in interburst interval were measured.
FIELD EPSP RECORDINGS: Field EPSPs were obtained from CA3-CA1 synapses following 0.1 hertz evoked stimulation. Changes in peak amplitude of the field EPSPs were measured. 1. Alkalosis increases burst probability of the CA3-CA1 network in a GABA-independent fasion.
2. Alkalosis can initiate spontaneous CA3 population bursts.
3. Alkalosis decreases the peak amplitude of the field EPSPs in CA3-CA1 synapses.
4. This effect is use-dependent and partially mimicked by the diminishment of extracellular Ca²⁺. The excitability of the CA3 network (increase in burst probability leading to increased epileptiform activity) is inversely proportional to available H⁺.
This finding is partially due to pH effects on availability of extracellular Ca²⁺.
These data are likely pertinent to the hyperventilation-induced changes in seizure threshold. (Supported by NINDS.)