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.

The slow afterhyperpolarization modulates high pH‐induced changes in the excitability of rat CA1 pyramidal neurons

“…1A). Consistent with previous findings (Balestrino & Somjen, 1988), the amplitude of the primary population spike evoked by the conditioning stimulus at pH o 7.7 (10.6 ± 1.5 mV; n = 10) was significantly larger than that observed in the same slices at pH o 7.4 (Fig. 1B).…”

“…That a change in pH is responsible for the results obtained here is suggested by previous findings that reducing P co 2 at a constant [HCO 3 – ] o elicits the same effects on neuronal excitability as increasing [HCO 3 – ] o at a constant P co 2 (e.g. Aram & Lodge, 1987; Balestrino & Somjen, 1988; Schuchmann et al ., 2006). In addition, we have shown previously that the increase in the sAHP observed upon increasing pH o from 7.4 to 7.7 (by increasing [HCO 3 – ] o at a constant P co 2 ) is markedly attenuated by the inclusion of high concentrations of H + buffers in patch‐pipette solutions (Kelly & Church, 2004) and is not due to the reduction in [Cl – ] o consequent upon the increase in [HCO 3 – ] o (Church, 1999).…”

The slow afterhyperpolarization modulates high pH‐induced changes in the excitability of rat CA1 pyramidal neurons

“…1A). Consistent with previous findings (Balestrino & Somjen, 1988), the amplitude of the primary population spike evoked by the conditioning stimulus at pH o 7.7 (10.6 ± 1.5 mV; n = 10) was significantly larger than that observed in the same slices at pH o 7.4 (Fig. 1B).…”

“…That a change in pH is responsible for the results obtained here is suggested by previous findings that reducing P co 2 at a constant [HCO 3 – ] o elicits the same effects on neuronal excitability as increasing [HCO 3 – ] o at a constant P co 2 (e.g. Aram & Lodge, 1987; Balestrino & Somjen, 1988; Schuchmann et al ., 2006). In addition, we have shown previously that the increase in the sAHP observed upon increasing pH o from 7.4 to 7.7 (by increasing [HCO 3 – ] o at a constant P co 2 ) is markedly attenuated by the inclusion of high concentrations of H + buffers in patch‐pipette solutions (Kelly & Church, 2004) and is not due to the reduction in [Cl – ] o consequent upon the increase in [HCO 3 – ] o (Church, 1999).…”

Acidosis and blockade of orthodromic responses caused by anoxia in rat hippocampal slices at different temperatures.

“…Taking into account the slice thickness, probable tortuosity factor and extracellular volume fraction, a 10-15 mm excess of acid near the centre would be consistent with lactate production at a rate of 1-2,umol cm-3 min-' (in fair agreement with a previous estimate of 09 9,umol g-' min-'; Benjamin & Verjee, 1980). Although the increase in acidity at the higher temperature may contribute to the depression of the population spike (Balestrino & Somjen, 1988), the main factor is likely to be poorer synchronization of the briefer unitary spikes (Thompson, Masukawa & Prince, 1985).…”

“…As reported previously (Balestrino & Somjen, 1988;Walz, 1989), the interstitial pH (pH.) at the start or end of recording was consistently more acid (by 0-1-0-2 pH Fig.…”

“…Hence, the corresponding plot (filled circles) in Fig. 3D indicates a very weak correlation between EPSP amplitude and acidity (in agreement with Balestrino & Somjen, 1988).…”

The slow afterhyperpolarization modulates high pH‐induced changes in the excitability of rat CA1 pyramidal neurons

“…1A). Consistent with previous findings (Balestrino & Somjen, 1988), the amplitude of the primary population spike evoked by the conditioning stimulus at pH o 7.7 (10.6 ± 1.5 mV; n = 10) was significantly larger than that observed in the same slices at pH o 7.4 (Fig. 1B).…”

“…That a change in pH is responsible for the results obtained here is suggested by previous findings that reducing P co 2 at a constant [HCO 3 – ] o elicits the same effects on neuronal excitability as increasing [HCO 3 – ] o at a constant P co 2 (e.g. Aram & Lodge, 1987; Balestrino & Somjen, 1988; Schuchmann et al ., 2006). In addition, we have shown previously that the increase in the sAHP observed upon increasing pH o from 7.4 to 7.7 (by increasing [HCO 3 – ] o at a constant P co 2 ) is markedly attenuated by the inclusion of high concentrations of H + buffers in patch‐pipette solutions (Kelly & Church, 2004) and is not due to the reduction in [Cl – ] o consequent upon the increase in [HCO 3 – ] o (Church, 1999).…”

Acidosis and blockade of orthodromic responses caused by anoxia in rat hippocampal slices at different temperatures.

“…Taking into account the slice thickness, probable tortuosity factor and extracellular volume fraction, a 10-15 mm excess of acid near the centre would be consistent with lactate production at a rate of 1-2,umol cm-3 min-' (in fair agreement with a previous estimate of 09 9,umol g-' min-'; Benjamin & Verjee, 1980). Although the increase in acidity at the higher temperature may contribute to the depression of the population spike (Balestrino & Somjen, 1988), the main factor is likely to be poorer synchronization of the briefer unitary spikes (Thompson, Masukawa & Prince, 1985).…”

“…As reported previously (Balestrino & Somjen, 1988;Walz, 1989), the interstitial pH (pH.) at the start or end of recording was consistently more acid (by 0-1-0-2 pH Fig.…”

“…Hence, the corresponding plot (filled circles) in Fig. 3D indicates a very weak correlation between EPSP amplitude and acidity (in agreement with Balestrino & Somjen, 1988).…”

The slow afterhyperpolarization modulates high pH‐induced changes in the excitability of rat CA1 pyramidal neurons

“…1A). Consistent with previous findings (Balestrino & Somjen, 1988), the amplitude of the primary population spike evoked by the conditioning stimulus at pH o 7.7 (10.6 ± 1.5 mV; n = 10) was significantly larger than that observed in the same slices at pH o 7.4 (Fig. 1B).…”

“…That a change in pH is responsible for the results obtained here is suggested by previous findings that reducing P co 2 at a constant [HCO 3 – ] o elicits the same effects on neuronal excitability as increasing [HCO 3 – ] o at a constant P co 2 (e.g. Aram & Lodge, 1987; Balestrino & Somjen, 1988; Schuchmann et al ., 2006). In addition, we have shown previously that the increase in the sAHP observed upon increasing pH o from 7.4 to 7.7 (by increasing [HCO 3 – ] o at a constant P co 2 ) is markedly attenuated by the inclusion of high concentrations of H + buffers in patch‐pipette solutions (Kelly & Church, 2004) and is not due to the reduction in [Cl – ] o consequent upon the increase in [HCO 3 – ] o (Church, 1999).…”

Acidosis and blockade of orthodromic responses caused by anoxia in rat hippocampal slices at different temperatures.

“…Taking into account the slice thickness, probable tortuosity factor and extracellular volume fraction, a 10-15 mm excess of acid near the centre would be consistent with lactate production at a rate of 1-2,umol cm-3 min-' (in fair agreement with a previous estimate of 09 9,umol g-' min-'; Benjamin & Verjee, 1980). Although the increase in acidity at the higher temperature may contribute to the depression of the population spike (Balestrino & Somjen, 1988), the main factor is likely to be poorer synchronization of the briefer unitary spikes (Thompson, Masukawa & Prince, 1985).…”

“…As reported previously (Balestrino & Somjen, 1988;Walz, 1989), the interstitial pH (pH.) at the start or end of recording was consistently more acid (by 0-1-0-2 pH Fig.…”

“…Hence, the corresponding plot (filled circles) in Fig. 3D indicates a very weak correlation between EPSP amplitude and acidity (in agreement with Balestrino & Somjen, 1988).…”