Alkaline extracellular pH shifts generated by two transmitter-dependent mechanisms

1992 ◽  
Vol 70 (S1) ◽  
pp. S286-S292 ◽  
Author(s):  
M. Chesler ◽  
J. C. T. Chen

Recent studies of the effect of γ-aminobutyric acid (GABA) on brain extracellular pH are reviewed. Experiments were performed on isolated turtle cerebellum, using double-barrelled pH-sensitive microelectrodes. Superfusion of GABA (1 mM) caused a rapid extracellular alkaline shift accompanied by a rise in extracellular K+. Washout of GABA was often associated with an acid rebound, concomitant with an undershoot of extracellular K+. The GABA-evoked alkaline shift was blocked by picrotoxin and mimicked by the GABA-A agonists isoguvacine and muscimol. The response persisted in the nominal absence of extracellular calcium, but it was reversibly abolished in nominally bicarbonate free media. In contrast, extracellular alkaline shifts evoked by repetitive stimulation of the parallel fibers were amplified in bicarbonate-free media and were insensitive to picrotoxin. These results indicate the existence of separate, transmitter-dependent mechanisms of extracellular alkalinization: (i) a GABA-A receptor mediated process, most likely associated with efflux of bicarbonate ions across GABA-A anion channels and (ii) a bicarbonate-independent process associated with excitatory synaptic transmission.Key words: GABA, bicarbonate, extracellular pH, alkaline shift.

1998 ◽  
Vol 79 (5) ◽  
pp. 2730-2748 ◽  
Author(s):  
Maxim Bazhenov ◽  
Igor Timofeev ◽  
Mircea Steriade ◽  
Terrence J. Sejnowski

Bazhenov, Maxim, Igor Timofeev, Mircea Steriade, and Terrence J. Sejnowski. Cellular and network models for intrathalamic augmenting responses during 10-Hz stimulation. J. Neurophysiol. 79: 2730–2748, 1998. Repetitive stimulation of the thalamus at7–14 Hz evokes responses of increasing amplitude in the thalamus and the areas of the neocortex to which the stimulated foci project. Possible mechanisms underlying the thalamic augmenting responses during repetitive stimulation were investigated with computer models of interacting thalamocortical (TC) and thalamic reticular (RE) cells. The ionic currents in these cells were modeled with Hodgkin-Huxley type of kinetics, and the results of the model were compared with in vivo thalamic recordings from decorticated cats. The simplest network model demonstrating an augmenting response was a single pair of coupled RE and TC cells, in which RE-induced inhibitory postsynaptic potentials (IPSPs) in the TC cell led to progressive deinactivation of a low-threshold Ca2+ current. The augmenting responses in two reciprocally interacting chains of RE and TC cells depended also on γ-aminobutyric acid-B (GABAB) IPSPs. Lateral GABAA inhibition between identical RE cells, which weakened bursts in these cells, diminished GABAB IPSPs and delayed the augmenting response in TC cells. The results of these simulations show that the interplay between existing mechanisms in the thalamus explains the basic properties of the intrathalamic augmenting responses.


1992 ◽  
Vol 67 (1) ◽  
pp. 29-36 ◽  
Author(s):  
J. C. Chen ◽  
M. Chesler

1. Alkaline extracellular pH transients evoked by afferent stimulation, and local pressure ejection of glutamate and gamma-aminobutyric acid (GABA), were studied in the CA1 region of rat hippocampal slices. Amino acid-evoked responses were obtained by use of a dual micromanipulator, with the tip of a double-barreled pH-sensitive microelectrode positioned 50 microns from a pressure ejection pipette. 2. At 31 degrees C, in Ringer solutions buffered with 26 mM HCO3- and 5% CO2, mean extracellular pH in submerged 300-microns slices was 7.15 +/- 0.12 (n = 27 slices), at a tissue depth of approximately 150 microns. In Ringer buffered with 35 mM HCO3- and 5% CO2, extracellular pH was 7.29 +/- 0.10 (n = 19 slices). 3. Repetitive stimulation of the Schaffer collaterals caused an extracellular alkaline shift in stratum oriens, pyramidale, and radiatum, averaging 0.05 +/- 0.03 pH units among all regions (n = 138), with a maximum response of 0.16 pH units. Alkaline transients of similar appearance were obtained by local ejection of glutamate (0.01-0.12 pH units, n = 110) and GABA (0.01-0.18 pH units, n = 137). Control ejection of these amino acids into dilute agar caused only small acid shifts. 4. Superfusion of 100 microM picrotoxin abolished the GABA-evoked alkaline shift but failed to inhibit the Schaffer collateral- and glutamate-evoked alkalinizations. 5. Superfusion of 10(-5)-10(-3) M acetazolamide acidified the baseline by 0.05-0.10 pH units and amplified the Schaffer collateral- and glutamate-evoked alkaline shifts.(ABSTRACT TRUNCATED AT 250 WORDS)


1989 ◽  
Vol 62 (6) ◽  
pp. 1225-1236 ◽  
Author(s):  
S. M. Gurahian ◽  
S. H. Chandler ◽  
L. J. Goldberg

1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC-Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation.


1959 ◽  
Vol 1 (6) ◽  
pp. 534-555 ◽  
Author(s):  
P.O. Bishop ◽  
W. Burke ◽  
W.R. Hayhow

1975 ◽  
Vol 38 (6) ◽  
pp. 1390-1394 ◽  
Author(s):  
F. Emonet-Denand ◽  
Y. Laporte

Of 32 cat peroneus brevis spindles, 23 (72%) were found to be supplied by a least 1 skeletofusimotor or beta-axon. A motor axon was identified as skeletofusimotor when repetitive stimulation of it elicited both the contraction of extrafusal muscle fibers and as acceleration of the discharge of primary ending, which persisted after selective block of the neuromuscular junctions of extrafusal muscle fibers. The block was obtained by stimulating single axons at 400-500/s for a few seconds. Of 135 axons supplying extrafusal muscle fibers, 24 (18%) were shown to be beta-axons; 22 beta-axons had conduction velocities ranging from 45 to 75 m/s. All but three beta-axons increased the dynamic sensitivity of primary endings. Beta-innervated spindles may also be supplied by dynamic gamma-axons.


1987 ◽  
Vol 89 (2) ◽  
pp. 185-213 ◽  
Author(s):  
S Grinstein ◽  
S Cohen

The effect of elevating cytoplasmic Ca2+ [( Ca2+]i) on the intracellular pH (pHi) of thymic lymphocytes was investigated. In Na+-containing media, treatment of the cells with ionomycin, a divalent cation ionophore, induced a moderate cytoplasmic alkalinization. In the presence of amiloride or in Na+-free media, an acidification was observed. This acidification is at least partly due to H+ (equivalent) uptake in response to membrane hyperpolarization since: it was enhanced by pretreatment with conductive protonophores, it could be mimicked by valinomycin, and it was decreased by depolarization with K+ or gramicidin. In addition, activation of metabolic H+ production also contributes to the acidification. The alkalinization is due to Na+/H+ exchange inasmuch as it is Na+ dependent, amiloride sensitive, and accompanied by H+ efflux and net Na+ gain. A shift in the pHi dependence underlies the activation of the antiport. The effect of [Ca2+]i on Na+/H+ exchange was not associated with redistribution of protein kinase C and was also observed in cells previously depleted of this enzyme. Treatment with ionomycin induced significant cell shrinking. Prevention of shrinking largely eliminated the activation of the antiport. Moreover, a comparable shrinking produced by hypertonic media also activated the antiport. It is concluded that stimulation of Na+/H+ exchange by elevation of [Ca2+]i is due, at least in part, to cell shrinking and does not require stimulation of protein kinase C.


2001 ◽  
Vol 15 (6) ◽  
pp. 1089-1091 ◽  
Author(s):  
ARTUR MAYERHOFER ◽  
BARBARA HÖHNE-ZELL ◽  
KATIA GAMEL-DIDELON ◽  
HEIKE JUNG ◽  
PETER REDECKER ◽  
...  

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