Intra- and extracellular pH of the brain in vivo studied by 31P-NMR during hyper- and hypocapnia.

Studies were performed to determine the pH relationships among the extracellular, intracellular, and arterial blood compartments in the brain in vivo. Resolution of the extracellular monophosphate resonance peak from the intracellular peak in 31P nuclear magnetic resonance (NMR) spectra of sheep brain with the calvarium intact enabled pH measurement in these respective compartments. Sheep were then subjected to both hyper- and hypoventilation, which resulted in a wide range of arterial PCO2 and pH values. Linear regression analysis of pH in these compartments yielded slopes of 0.56 +/- 0.05 for extracellular pH (pHe) vs. arterial pH, 0.43 +/- 0.078 for intracellular pH (pHi) vs. pHe, and 0.23 +/- 0.056 for pHi vs. arterial pH. These data indicate that CO2 buffering capacity is different and decreases from the intracellular to extracellular to arterial blood compartments. Separation of the extracellular space from the vascular space may be a function of the blood-brain barrier, which contributes to the buffering capability of the extracellular compartment. A marked decrease in the pH gradient between the extracellular and intracellular space occurs during hypercarbia and may influence mechanisms of central respiratory control.     

Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography. Contrary to the only previous study in humans, which reported an insignificant 3% reduction in CMRO2 during sleep, we found a deep-sleep-associated statistically highly significant 25% decrease in CMRO2, a magnitude of depression according with studies of glucose uptake and reaching levels otherwise associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep.     

Chloride conductance of the Amphiuma red cell membrane

Summary Like most other red cells, the giant erythrocytes ofAmphiuma means possess a system for rapid exchange of chloride across the membrane. Also, there are indications that the net transport of chloride in these cells is slow. The size ofAmphiuma erythrocytes allows direct measurements of membrane potential with microelectrodes. The present work exploits the possibility that such measurements can be used to give a quantitative estimate of the chloride conductance (G _Cl) of the Amphiuma red cell membrane. The membrane potential was measured as a function of extracellular chloride concentration (5–120mM), using an impermeant anion (Para-amino-hippurate) as a substitute. Furthermore, the effect of different pH values (6.0–7.2) was studied. For each extracellular chloride concentration the membrane potential was determined at a pH at which hydroxyl, hydrogen, and bicarbonate ions were in electrochemical equilibrium. From these membrane potentials and the corresponding chloride concentrations in the medium (at constant intracellular ion concentrations), theG _Cl of the membrane was calculated to be 3.9×10^–7 {ie27-1} cm^–2. This value is some six orders of magnitude smaller than that calculated from the rate of tracer exchange under equilibrium conditions. The experimental strategy used gives the value for a partial transference number which takes into account only ions which arenot in electrochemical equilibrium. Whereas this approach gives a value forG _Cl, it does not permit calculation of the overall membrane conductance. From the calculated value ofG _Cl it is possible to estimate that the maximal value of the combined conductances of hydroxyl (or proton) and bicarbonate ions is 0.6×10^–7 {ie27-2} cm^–2. The large discrepancy between the rate of exchange of chloride and its conductance is in agreement with measurements on human and sheep red cells employing the ionophore valinomycin to increase the potassium conductance of the membrane. The results in the present study were, however, obtained without valinomycin and an accompanying assumption of a constant field in the membrane. Therefore, the present measurements give independent support to the above mentioned conclusions.     

Mental stress and cognitive performance do not increase overall level of cerebral O2 uptake in humans.

We measured cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral lactate output during rest, during the execution of mental arithmetic, and during mental stress induced by physical and psychological annoyance. Measurements were performed in healthy volunteers by use of the Kety-Schmidt technique with 133Xe as the inert gas. Electroencephalographic desynchronization and highly significant increases in plasma catecholamines and heart rate verified that the test measurements were performed during conditions differing distinctly from the resting state. In accordance with an earlier study (Sokoloff et al. J. Clin. Invest. 34: 1101-1108, 1985), a minimal and nonsignificant 1% reduction of global CMRO2 during mental arithmetic was observed, signifying that this form of mental activation was unassociated with any detectable increase in overall cerebral synaptic activity. Mental stress induced a slight but highly significant (P less than 0.002) 6% reduction in global CMRO2. This finding is in contrast to results from earlier investigations and contradicts the generally accepted notion of an association between mental arousal and a diffuse upregulation of cerebral synaptic activity. During mental arithmetic and mental stress, cerebral lactate output increased by 207 and 344%, respectively, but because of large individual variations in the measured responses, the elevations reached statistical significance only during mental arithmetic.     

Effect of antihistamines and chlorpromazine on the calcium-induced hyperpolarization of the Amphiuma red cell membrane

1. 1. It has previously been demonstrated that an increase in extracellular Ca²⁺ concentration induces a transient increase in K⁺ permeability and associated hyperpolarization of the red cell membrane of the giant salamander, Amphiuma means. This phenomenon is analogous to the Ca²⁺-induced KCl loss observed in ATP-depleted human red cells and red cell ghosts.

2. 2. Histamine, which enhances the Ca²⁺-induced K⁺ loss from depleted human red cells, is without effect on this Ca²⁺-induced hyperpolarization of Amphiuma red cells.

3. 3. Promethazine (10 μM) and mepyramine (1 mM), which inhibit the Ca²⁺-induced K⁺ loss in depleted human red cells, also block the Ca²⁺-related hyperpolarization of Amphiuma erythrocytes.

4. 4. Chlorpromazine (25 μM), despite being a weak antihistamine, is equally effective in blocking the Ca²⁺-induced hyperpolarization of Amphiuma red cells.

5. 5. Ionophore A23187 causes a large and sustained Ca²⁺/K⁺-dependent hyperpolarization even in the presence of normal (1.8 mM) concentrations of Ca²⁺. This hyperpolarization is relatively insensitive to chlorpromazine and promethazine.

6. 6. The inhibition of the Ca²⁺-induced hyperpolarization of the Amphiuma red cell membrane by chlorpromazine and promethazine may be related to their properties as local anaesthetics.

A family with a high risk of segregation for an autosomal unbalanced reciprocal translocation

Summary A family with autosomal reciprocal translocation t(4;13) (q25;q31) with a sibship comprising 2 children with unbalanced karyotypes, der(13) partial trisomy 4q, 1 child with the balanced translocation, and 2 abortions were studied. The segregation risk of unbalanced derivation in reciprocal translocations is discussed. The clinical picture of the 2 children with partial trisomy 4q is compared with similar cases.