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C R Rose

Publications and source records attributed to C R Rose.

25 records · Page 2Linked to original sources
PubMed1996

pH regulation and proton signalling by glial cells.

The regulation of H+ in nervous systems is a function of several processes, including H+ buffering, intracellular H+ sequestering, CO2 diffusion, carbonic anhydrase activity and membrane transport of acid/base equivalents across the cell membrane. Glial cells participate in all these processes and therefore play a prominent role in shaping acid/base shifts in nervous systems. Apart from a homeostatic function of H(+)-regulating mechanisms, pH transients occur in all three compartments of nervous tissue, neurones, glial cells and extracellular spaces (ECS), in response to neuronal stimulation, to neurotransmitters and hormones as well as secondary to metabolic activity and ionic membrane transport. A pivotal role for H+ regulation and shaping these pH transients must be assigned to the electrogenic and reversible Na(+)-HCO3-membrane cotransport, which appears to be unique to glial cells in nervous systems. Activation of this cotransporter results in the release and uptake of base equivalents by glial cells, processes which are dependent on the glial membrane potential. Na+/H+ and Cl-/HCO3-exchange, and possibly other membrane carriers, accomplish the set of tools in both glial cells and neurones to regulate their intracellular pH. Due to the pH dependence of a great variety of processes, including ion channel gating and conductances, synaptic transmission, intercellular communication via gap junctions, metabolite exchange and neuronal excitability, rapid and local pH transients may have signalling character for the information processing in nervous tissue. The impact of H+ signalling under both physiological and pathophysiological conditions will be discussed for a variety of nervous system functions.

Animals↗
PubMed1995

Activity-induced Ca2+ transients in nerve and glial cells in the leech CNS.

We have measured activity-induced Ca2+ transients in Retzius neurones, neuropile glial cells, and extracellular spaces of isolated ganglia of the leech Hirudo medicinalis using the fluorescent dye fura-2 and Ca(2+)-sensitive microelectrodes. Neuronal activity, induced by electrical side nerve stimulation (20 Hz/1 min), elicited transient rises of intracellular Ca2+ in both neurones and glial cells, which amounted to 24 +/- nM (n = 15) and 17 +/- 14 nM (n = 7), respectively. The extracellular Ca2+ declined by 160 +/- 73 microM (n = 6) during stimulation. Intra- and extracellular Ca2+ transients were reduced by the glutamate/kainate receptor blocker CNQX (6-cyano-7-dinitroquinozaline-2,3-dione; 50 microM). Our results show that neuronal activity evokes Ca2+ signals not only in neurones, but also in glial cells and suggest that these Ca2+ transients are partly mediated via activation of glutamate/kainate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Stimulus-evoked changes of extra- and intracellular pH in the leech central nervous system. I. Bicarbonate dependence.

1. We have measured the effect of repetitive electrical nerve root stimulation on the extracellular potassium activity (aKe) and the extracellular pH (pHe) and intracellular pH (pHi) in segmental ganglia of the leech Hirudo medicinalis with double-barreled K(+)- and pH-sensitive microelectrodes. To investigate the influence of CO2/HCO3-, we compared the stimulus-evoked changes in aKe, pHe, and pHi in the presence and absence of 5% CO2-24 mM HCO3- in the saline. 2. An electrical nerve root stimulation at 20-30 Hz for 1 min caused a rapid increase of 1.11 +/- 0.79 (SD) mM in aKe, followed by an aKe undershoot of 0.17 +/- 0.15 mM when the stimulation was discontinued (n = 6). aKe transients were not significantly affected by CO2/HCO3-. 3. In 5 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered, nominally CO2/HCO3(-)-free saline, low stimulus intensities or stimulus durations up to a few seconds resulted in a fast alkaline pHe transient. This alkalinization was followed by a larger and longer-lasting extracellular acidification when the stimulation was intensified and prolonged. A stimulation at 20 Hz, 5 V for 1 min caused an average alkaline shift of 0.083 +/- 0.055 pH units, followed by an acidosis of 0.079 +/- 0.038 pH units (n = 63). A change from 5 mM HEPES-buffered saline to 20 mM HEPES-buffered saline attenuated the stimulus-evoked pHe transients by 50-60%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Stimulus-evoked changes of extra- and intracellular pH in the leech central nervous system. II. Mechanisms and maintenance of pH homeostasis.

1. We have studied extracellular pH (pHe) and intracellular pH (pHi) changes evoked by repetitive electrical side nerve stimulation (20 Hz, 1 min) in segmental ganglia of the leech Hirudo medicinalis using double-barreled, pH-sensitive microelectrodes to elucidate the involvement of neurotransmitters, of carbonic anhydrase, and of active acid/base transport on the extracellular H+ homeostasis. In saline buffered with 5% CO2-24 mM HCO3-, the stimulation induced a small and brief alkalinization followed by an acidification in the extracellular spaces (ECS), whereas neurons acidified and glial cells alkalinized (see previous paper). 2. Blocking synaptic transmitter release by superfusion with 20 mM Mg2+ saline (CO2/HCO3(-)-free) led to a reversible reduction of both activity-induced pHe changes by approximately 90% and to a complete suppression of the intracellular acidification of neurons. After application of the glutamate/kainate receptor blocker 6-cyano-7-dinitroquinozaline-2,3-dione (CNQX, 50 microM) to CO2/HCO3(-)-free saline, the stimulus-evoked pHe changes were reversibly reduced. The gamma-aminobutyric acid-A (GABAA) receptor antagonist picrotoxin (50 microM) led to an amplification of the extracellular alkalinization in the presence of CO2/HCO3-. Bath application of the excitatory transmitter agonists carbachol or kainate to CO2/HCO3(-)-free saline induced biphasic alkaline-acid transients in the ECS; the inhibitory transmitters GABA and serotonin had no detectable effects on the pHe (saline buffered with CO2/HCO3-).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Evidence that glial cells modulate extracellular pH transients induced by neuronal activity in the leech central nervous system.

1. The role of the giant neuropile glial cells in the buffering of activity-related extracellular pH changes was studied in segmental ganglia of the leech Hirudo medicinalis L. using pH-sensitive microelectrodes and a slow, two-electrode voltage-clamp system. Neuronal activity was induced by electrical stimulation of a ganglionic side nerve (20 Hz, 1 min). 2. In CO2-HCO3(-)-buffered saline the glial cells were depolarized by 6.5 +/- 2.3 mV and alkalinized by 0.024 +/- 0.006 pH units (mean +/- SD) during the stimulation. The stimulation induced an acidification of 0.032 +/- 0.006 pH units in the extracellular spaces (ECS). 3. Voltage clamping the glial cells suppressed the stimulus-induced glial depolarization and turned the intraglial alkalinization into an acidification of 0.045 +/- 0.021 pH units (n = 6) that closely resembled the acidification observed in the presence of the anion transport blocker DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, 0.5 mM), and in CO2-HCO(3-)-free saline. 4. Voltage clamping the glial cell resulted in the appearance of a distinct stimulus-induced extracellular alkalinization of 0.024 +/- 0.013 pH units at the onset of the stimulation, as also observed during DIDS application and in the absence of CO2-HCO3-. 5. The results suggest that glial uptake of bicarbonate is mediated by depolarization-induced activation of the electrogenic Na(+)-HCO3- cotransport, which suppresses the profound alkalinization of the ECS during neuronal activity. This is the first direct evidence the glial cells actively modulate extracellular pH changes in a voltage-dependent manner.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗