Concentration of carbon dioxide, interstitial pH and synaptic transmission in hippocampal formation of the rat.

Abstract

SUMMARY1. Interstitial pH (pHO) was measured with ion-selective microelectrodes in the fascia dentata of rats anaesthetized with urethane,while C02 levels were controlled by varying pulmonary ventilation and C02 content of inspired air. In the CAI sector of hippocampal tissue slices in vitro pH. was similarly measured and altered by varying C02 in the gas phase, or by adding HCI or NaOH to the artificial cerebrospinal fluid (ACSF) of the bath, or by changing the concentration of HCO3-.2. Orthodromically evoked compound action potentials ('population spikes') were depressed in hypercapnia and increased in hypocapnia. In the fascia dentata of intact brains the population spike of the granule cells varied on average by more than 40 % of control amplitude for each 0X1 change of pHo. In the CAI zone of tissue slices in vitro, the change of population spike amplitude was approximately 30 % per pH change of 041 caused by altered C02 or HCOG-concentration, but only about 15 % per pH change of 0-1 when HCl or NaOH were administered.3. In anaesthetized rats the focal synaptic potential (FEPSP) evoked by a given stimulus intensity was weakly influenced by varying [C02]; in tissue slices weak effects on FEPSP were inconsistent. In hippocampus both in situ and in vitro the population spike triggered by a given magnitude of FEPSP increased in hypocapnia and decreased in hypercapnia. This suggests that the main effect of C02 is on the electric excitability of postsynaptic cells, with minor or no effect on transmitter release and on the interaction of the transmitter with its receptors.4. Hypercapnia of anaesthetized rats was usually associated with a slight increase of [K+]. in the fascia dentata. Tissue [Ca2+]0 changed little and not consistently.Neither of these two ions, nor concomitant changes of blood pressure or tissue partial pressure of oxygen, (Pt,02), could account for the effects of pH on neuronal excitability. 5. The results show that increasing the extracellular concentration of H+ ions has a moderately depressant effect on the firing threshold of hippocampal neurones. The more powerful effects of elevated [C02] and of lowered [HC03-j may probably be explained by a direct effect on the neuronal membrane. The brain, by regulating breathing, controls its own excitability.

Protons Trap NR1/NR2B NMDA Receptors in a Nonconducting State

“…Because neuronal injury during both seizure and ischemia is associated with glutamate release (Hirano et al, 2003) and NMDA receptor activation, mild acidification of the extracellular space in the penumbra might be expected to limit the extent of glutamate-induced neurotoxicity, although acidification in the infarct core can be harmful. In support of this hypothesis, decreasing extracellular pH to a level observed during ischemia reduces the contribution of NMDA receptors to neuronal death in cortical cultures (Giffard et al, 1990;Kaku et al, 1993) and can increase seizure threshold in vivo (Balestrino and Somjen, 1988).…”

“…Interstitial pH undergoes multiphasic changes during normal synaptic transmission and much larger changes during seizure activity and ischemia, during which pH levels can fall by 0.2-0.6 pH units (Siesjo, 1985;Balestrino and Somjen, 1988;Nedergaard et al, 1991;Chesler and Kaila, 1992). Because neuronal injury during both seizure and ischemia is associated with glutamate release (Hirano et al, 2003) and NMDA receptor activation, mild acidification of the extracellular space in the penumbra might be expected to limit the extent of glutamate-induced neurotoxicity, although acidification in the infarct core can be harmful.…”

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

“…The exact mechanisms by which tissue pH and neuronal density may influence each other are not known yet. Changes in the physiological parameters of neurons and glial cells, and alterations in glutamate uptake and calcium metabolism, have been associated with changes in the intracellular or extracellular tissue pH (Balestrino and Somjen, 1988;Caspers and Speckmann, 1972;Dipolo and Beauge, 1982;Goldman et al, 1989;Gruol et al, 1980;Pappas et al, 1994;Robello et al, 1994;Takahashi et al, 1995). It is also known that changes in tissue pH are associated with certain pathological conditions such as ischemia or head injury (Billups and Attwell, 1996;Cadoux-Hudson et al, 1990;Smith et al, 1986).…”

Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability

“…Commonly, a rise in brain pH is associated with increased neuronal excitability, whereas a fall in pH has been shown to have the opposite effect (9,10). Recently, hyperthermia-induced respiratory alkalosis was demonstrated to trigger ictal activity in a febrile seizure model (11).…”