Coerulospinal enhancement of repetitive firing with correlative changes in postspike afterhyperpolarization of cat spinal motoneurons

The present study was aimed at determining if inputs from the locus coeruleus (LC) have any effect on repetitive firing of ventral horn motoneurons in cats. In hindlimb flexor and extensor motoneurons stimulated intrasomatically with current below the threshold for repetitive discharges, added LC-evoked excitatory post-synaptic potentials (EPSPs) were consistently found to produce repetitive firing, suggesting a lowering in the repetitive firing threshold attributable to excitatory LC inputs. With those extensor motoneurons showing episodic, self-sustained firing, LC-EPSPs introduced during the quiescent period were capable of starting a continuous discharge with rhythmic frequencies higher than the spontaneous activity. In some of these cells, intracellularly applied hyperpolarizing current was able to stop the spontaneous discharges. Subsequently, LC stimuli were found to reinitiate repetitive discharges, thus counteracting the ongoing suppression of the motoneurons. Quantitative analysis of the single-spike afterhyperpolarization (AHP) indicated a consistent reduction in its amplitude and time course (duration, time-to-peak, half-decay time) for flexor and extensor motoneurons in response to LC conditioning stimuli. Present results suggest an excitatory LC action on the repetitive discharges of cat motoneurons accompanied by a concurrent decrease in the amplitude and time course of the single-spike AHPs.     

Glucagon-like peptide-1 modulates synaptic transmission to identified pancreas-projecting vagal motoneurons

Using a brainstem slice preparation, we aimed to study the pre- and postsynaptic effects of glucagon-like peptide-1 (GLP-1) on synaptic transmission to identified pancreas-projecting vagal motoneurons. Following blockade of GABAergic mediated currents with bicuculline, perfusion with 100 nM GLP-1 increased both amplitude and frequency of excitatory postsynaptic currents (EPSCs) in 21 of 52 neurons. Perfusion with the GLP-1 selective agonist exendin-4 (100 nM), also increased the frequency of spontaneous EPSCs, while pretreatment with the GLP-1 selective antagonist, exendin 9-39, prevented the effects of GLP-1. In the presence of kynurenic acid to block ionotropic glutamatergic currents, perfusion with GLP-1 increased the frequency of inhibitory postsynaptic currents (IPSCs) in 28 of 74 neurons; in 14 of these responsive neurons, GLP-1 also increased IPSC amplitude, indicating actions at both pre- and postsynaptic sites. Perfusion with exendin-4 increased the frequency of spontaneous IPSCs, while pretreatment with exendin 9-39 prevented the effects of GLP-1. These results suggest that GLP-1 modulates both excitatory and inhibitory synaptic inputs to pancreas-projecting vagal motoneurons.     

Presynaptic serotonergic modulation of spontaneous and miniature synaptic activity in frog lumbar motoneurons

The effects of serotonin (5-HT, 30 μM) on spontaneous and miniature synaptic activity in lumbar motoneurons from the isolated Rana ridibunda spinal cord were investigated using intracellular recording. 5-HT increased the frequency of spontaneous (sPSPs) and miniature postsynaptic potentials (mPSPs). The effect of 5-HT on different subpopulations of mPSPs was multidirectional: it increased the frequency of glutamatergic excitatory mPSPs by 18% and decreased the frequency of glycinergic inhibitory mPSPs by 28%, but had no effect on the frequency of GABAergic inhibitory mPSPs. The amplitude and kinetic parameters of any subpopulation of mPSPs did not change. The data obtained show that 5-HT regulates the probability of glutamate and glycine release from the presynaptic terminals ending at frog spinal motoneurons. 5-HT shifts the balance between synaptic excitation and inhibition in the spinal neural network toward excitation. Thus, 5-HT participates in control of motor output and provides its facilitation.     

Effect of local depression of inhibition on electrical activity of the spinal cord

The dorsal cord, dorsal root, and focal potentials in response to peripheral nerve stimulation were investigated in rats with local depression of inhibition in the left or right half of the lumbar segments produced by the action of tetanus toxin. The investigation was carried out at the stage of poisoning when excitation of the neuron population with disturbed inhibition caused generalized excitation of spinal and bulbar motoneurons. Experiments on spinal animals showed that if a cutaneous nerve is stimulated on the side affected by the toxin these responses have a greater amplitude and a much longer duration than those evoked by stimulation of the opposite nerve or responses in healthy rats. The maximal increase in amplitude and duration of the negative component of the focal potential corresponding to the time of the increased P wave of the dorsal cord potential was found in the ventral quadrant on the side affected by the toxin. Besides evoked focal potentials, spontaneous rhythmic negative waves also were recorded in this area. The mechanisms of spread of seizure activity from the focus of depressed inhibition are discussed and the structures generating spreading seizure activity are identified.     

Effect of calcium deficiency and addition of calcium antagonists on motoneuron synaptic potentials of isolated Emys orbicularis turtle spinal cord

In experiments carried out on the isolated spinal cord of the tortoise Emys orbicularis postsynaptic potentials produced in spinal motoneurons by stimulation of the descending tracts and dorsal roots were investigated by means of the intracellular recording technique. Postsynaptic potentials were completely and reversibly blocked in Ca2+-free solutions containing 5.0 mM Mg2+ or 2.0 mM Mn2+. The amplitude and frequency of spontaneous synaptic potentials were also reduced under these conditions. The effect of Ca2+-free medium indicates that the synaptic transmission in these synapses is mediated by chemical mechanism.     

Modulation of miniature inhibitory potentials in motoneurons of the turtle spinal cord by group II metabotropic glutamate receptors

The role of group II metabotropic glutamate receptors (mGluRs) in modulation of inhibitory synaptic activity was studied by intracellular recording of motoneuron miniature inhibitory spontaneous postsynaptic potentials (mIPSPs) in isolated lumbar segments of the turtle spinal cord in the medium containing TTX, CNQX, AP-5. The ratio of mIPSPs with fast and slow kinetics (83% vs 17%) is in accordance with the ratio shown for glycine- and GABA-mediated IPSP or IPSCs (Jones et al., 1988; Gao et al., 2001). In the majority of investigated motoneurons, the selective group II mGluRs antagonist EGLU (100-250 microM) increased the frequency of mIPSPs by 106.6 +/- 74.4% (n = 9) without affecting average amplitude, suggesting a presynaptic site of mGluRs action providing for the transmitter release reduction. The analysis of EGLU action on mIPSPs with different time courses (selection by half-width) showed that the frequency of inhancement of miniature inhibitory activity is caused by predominantly short-duration mIPSPs (ba 84.0 +/- 18.2%; n = 9), which are probably glycineergic. However, EGLU did not influence the mIPSPs frequency under condition of GABA-receptor blockade by bicuculline (20 microM). This fact suggest that group II mGluRs could modulate glycinergic transmission to the turtle spinal motoneurons on the necessary condition that GABergic system is active.     

Electrical Events Correlated with Contractile Vacuole Activity in the Suctorian, Heliophrya

SYNOPSIS. The surface membrane potentials of suctorian genus Heliophrya were studied with intracellular electrodes. Resting membrane potentials averaged -32 mV, and spontaneous depolarizing potentials occurring at apparently random intervals and having a variety of waveforms were routinely observed. Such spontaneous potentials were correlated in time with visually monitored contractile vacuole activity. Individual contractile vacuoles had unique, although somewhat variable, electrical signatures. In the presence of an intracellular electrode all vacuoles contracted independently, but at approximately the same frequency. The amplitude of the electrical potentials increased when the membrane was hyperpolarized and decreased when it was depolarized. The sign of such potentials reversed at between -10 mV and the zero membrane potential. A 20% decrease in the membrane resistance was measured at the peak of the spontaneous depolarizing potentials.     

Dual action of intracellularly released calcium on the quantal mediator secretion

The mice diaphragm muscle and microelectrode technique were used to check the influence of ryanodine (0.5 mcM) on spontaneous and evoked mediator release under conditions of potassium depolarization (8-16 mM [K+]ex or rhythmic (4-100 Hz) stimulation of motor nerve terminals. Weak tonic calcium loading (by muscle exposition to 8 mM [K+]ex) caused a two-fold frequency increase if miniature and plate potentials (MEPPs), which was returned to the basal level by subsequent application of ryanodine. This inhibitory effect of ryanodine was blocked by apamin (500 nM) a blocker of K+(Ca)-channels. A greater calcium load of terminals (in solution with 16 mM [K+]ex) caused a 15-fold increase of MEPPs frequency. Subsequent ryanodine application caused an additional 2-3-fold increase of MEPPs frequency. During rhythmic activity of motor synapses, ryanodine was able to decrease the amplitude of EPP by 60% at plateau phase at short low frequency (4 Hz) of discharges and to increase the amplitude of EPP by 60-150% at high frequency (70-100 Hz) of discharges. It is concluded that rynodine induced calcium release from intraterminal Ca2+-stores can influence dual: excitatory or inhibitory, action on spontaneous and evoked mediator release, due to different intraterminal calcium loads and regimen of synaptic activity.     

Acidosis facilitates spontaneous sarcoplasmic reticulum Ca2+ release in rat myocardium

Previous studies have shown that acidosis increases myoplasmic [Ca2+] (Cai). We have investigated whether this facilitates spontaneous sarcoplasmic reticulum (SR) Ca2+ release and its functional sequelae. In unstimulated rat papillary muscles, exposure to an acid solution (produced by increasing the [CO2] of the perfusate from 5 to 20%) caused a rapid increase in the mean tissue Cai, as measured by the photoprotein aequorin. This was paralleled by an increase in spontaneous microscopic tissue motion caused by localized Ca2+ myofilament interactions, as monitored in fluctuations in the intensity of laser light scattered by the muscle. In regularly stimulated muscles, acidosis increased the size of the Ca2+ transient associated with each contraction and caused the appearance of Cai oscillations in the diastolic period. In unstimulated single myocytes, acidosis depolarized the resting membrane potential by approximately 5 mV and enhanced the frequency of spontaneous contractile waves. The small sarcolemmal depolarization associated with each contractile wave increased and occasionally initiated spontaneous action potentials. In regularly stimulated myocytes, acidosis caused de novo spontaneous contractile waves between twitches; these waves were associated with a decrease in the amplitude of the subsequent stimulated twitch. Ryanodine (2 microM) abolished all evidence of spontaneous Ca2+ release during acidosis, markedly reduced the acidosis-induced increase in aequorin light, and reduced resting tension. We conclude that acidosis increases the likelihood for the occurrence of spontaneous SR Ca2+ release, which can cause spontaneous action potentials, increase resting tension, and negatively affect twitch tension.     

Role of GABA<Subscript>B</Subscript> receptor in the regulation of excitatory synaptic transmission in trigeminal motoneurons

The aim of the present study was to determine if excitatory synaptic transmission onto trigeminal motoneurons is subject to a presynaptic modulation by gamma-aminobutyric acid (GABA) via GABA(B) receptor in this system. Whole cell recordings were made from trigeminal motoneurons in longitudinal brain stem slices taken from 8-day-old rats. Monosynaptic excitatory postsynaptic potential (EPSP) activity was evoked by placing bipolar stainless steel electrodes dorsal-caudal to the trigeminal motor nucleus. Bath application of the GABA(B) receptor agonist, baclofen, produced a marked reduction in the mean amplitude and variance of evoked EPSPs and also increased the portion of transmission failures. It also produced a decrease in the frequency, but not in the mean amplitude, of spontaneous miniature EPSPs. Bath application of GABA(B) receptor antagonists 6-hydroxy-saclofen and CGP35348 increased both the amplitude and frequency of miniature EPSP activity. Taken together the above results suggest that the excitatory synaptic inputs onto trigeminal motoneurons are controlled by tonic presynaptic modulation by GABA(B) receptor.     

Effects of barium on isolated frog spinal cord

The effects of Ba2+ were studied in vitro on the isolated frog spinal cord. Ba2+ (25 microM-5 mM) caused a concentration-dependent depolarization of ventral (VR) and dorsal (DR) roots. TTX and Mg2+ substantially reduced the depolarization suggesting that interneuronal effects were involved. Ba2+ (25-500 microM) markedly increased the frequency and duration of spontaneous VR and DR potentials and substantially enhanced the duration (and frequently the amplitude) of VR and DR potentials evoked by DR stimulation. Higher concentrations of Ba2+ (1-5 mM) reduced both spontaneous and evoked potentials. Ba2+ (25-500 microM) enhanced the amount of K+ released by a DR volley and by application of L-glutamate and L-aspartate. The cation reduced VR and DR root depolarizations produced by elevated [K+]0. VR potentials induced by L-glutamate, L-aspartate, GABA and glycine and DR depolarizations caused by GABA were reduced by Ba2+. These results show that Ba2+ has complex actions on reflex transmission, interneuronal activity, the postsynaptic actions of excitatory and inhibitory amino acids and the evoked release of K+.     

Thyrotropin-releasing hormone mimics descending slow synaptic potentials in rat spinal motoneurons

Thyrotropin-releasing hormone (TRH) produced a depolarization in lumbar motoneurons of neonatal rats. The depolarization by TRH persisted after extracellular Ca2+ was replaced by Mg2+ or Mn2+, indicating its direct action upon motoneurons. Stimulation of the ventral descending tract at the lower thoracic segment evoked slow excitatory postsynaptic potentials (e.p.s.ps) lasting 20-30 s in every motoneuron. Both the TRH-induced depolarization and descending slow e.p.s.p. were accompanied by a decrease in input conductance of motoneurons. When the membrane potential of the motoneuron was shifted, both the TRH-induced depolarization and slow e.p.s.p. became larger in amplitude during depolarization and smaller during hyperpolarization. However, they could not be reversed in polarity by hyperpolarization. During the depolarization of motoneuron produced by TRH application, the slow e.p.s.p. was markedly reduced in amplitude, suggesting the involvement of identical ionic mechanisms in the two responses. After incubation of the isolated spinal cord with antisera to TRH, the depolarizing response produced by TRH as well as the descending slow e.p.s.p. was greatly diminished. In contrast, monosynaptic reflexes evoked by dorsal root stimulation remained unchanged under this condition. These results suggest that TRH serves as a neurotransmitter mediating the descending slow e.p.s.p. in motoneurons.     

Oscillatory zones and their role in normal and abnormal sheep purkinje fiber automaticity

The mechanisms by which low [K(+)](o) induces spontaneous activity was studied in sheep Purkinje fibers. Purkinje strands were superfused in vitro and membrane potentials were recorded by means of a microelectrode technique. The results show that low [K(+)](o) increases the slope and amplitude of early diastolic depolarization, sharpens the transition between early and late diastolic depolarizations, induces an after-potential and large pre-potentials through a negative shift of an oscillatory zone. Pre-potentials occur progressively sooner during diastole and merge with the after-potential to induce uninterrupted spontaneous discharge. During recovery, when the rate slows, after- and pre-potentials separate once more, the slower discharge decreasing the after-potentials but not the pre-potentials. Low [K(+)](o) has little effect on the plateau, but markedly slows phase 3 repolarization and may altogether prevent it. At depolarized levels, voltage oscillations, slow responses, sinusoidal fluctuations or quiescence may be present depending on voltage. During the recovery, a train of either sub-threshold oscillations or spontaneous action potentials appear towards the end of phase 3 repolarization. The cessation of the action potentials unmasks large sub-threshold oscillations, that occur in the oscillatory zone. Drive, high [Ca(2+)](o) and norepinephrine increase slope and amplitude of early diastolic depolarization as low [K(+)](o) does. In low [K(+)](o), Cs(+) prevents spontaneous discharge at polarized levels, but not the decrease in resting potential nor the onset of slow responses at depolarized levels. Cs(+) blocks the train of oscillations and of action potentials occurring during recovery. We conclude that low [K(+)](o) steepens early diastolic depolarization and increases its amplitude through an after-potential that results from an increased Ca(2+) load; allows the attainment of the threshold through Cs(+)-sensitive voltage oscillations which develop when the oscillatory zone is entered either by diastolic depolarization or by phase 3 repolarization; and causes voltage oscillations also at depolarized levels, but through a Cs(+)-insensitive different mechanism.     

Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats.

We tested two hypotheses: 1) that the spontaneous enhancement of phrenic motor output below a C2 spinal hemisection (C2HS) is associated with plasticity in ventrolateral spinal inputs to phrenic motoneurons; and 2) that phrenic motor recovery in anesthetized rats after C2HS correlates with increased capacity to generate inspiratory volume during hypercapnia in unanesthetized rats. At 2 and 4 wk post-C2HS, ipsilateral phrenic nerve activity was recorded in anesthetized, paralyzed, vagotomized, and ventilated rats. Electrical stimulation of the ventrolateral funiculus contralateral to C2HS was used to activate crossed spinal synaptic pathway phrenic motoneurons. Inspiratory phrenic burst amplitudes ipsilateral to C2HS were larger in the 4- vs. 2-wk groups (P<0.05); however, no differences in spinally evoked compound phrenic action potentials could be detected. In unanesthetized rats, inspiratory volume and frequency were quantified using barometric plethysmography at inspired CO2 fractions between 0.0 and 0.07 (inspired O2 fraction 0.21, balance N2) before and 2, 3, and 5 wk post-C2HS. Inspiratory volume was diminished, and frequency enhanced, at 0.0 inspired CO2 fraction (P<0.05) 2-wk post-C2HS; further changes were not observed in the 3- and 5-wk groups. Inspiratory frequency during hypercapnia was unaffected by C2HS. Hypercapnic inspiratory volumes were similarly attenuated at all time points post-C2HS (P<0.05), thereby decreasing hypercapnic minute ventilation (P<0.05). Thus increases in ipsilateral phrenic activity during 4 wk post-C2HS have little impact on the capacity to generate inspiratory volume in unanesthetized rats. Enhanced crossed phrenic activity post-C2HS may reflect plasticity associated with spinal axons not activated by our ventrolateral spinal stimulation.     

Protective effects of CB1 receptor agonist WIN 55.212-2 in seizure activity in the model of temporal lobe epilepsy

The influence of a low dose (1 microM, 2 microl) of nonselective agonist of cannabinoid CB1 receptor WIN 55.212-2 on seizure activity in different brain structures was investigated in waking guinea pigs. Changes in spontaneous local field potentials and seizure afterdischarges evoked by the electrical stimulation of the perforant path were recorded simultaneously in the hippocampus, entorhinal cortex, medial septal region, and amygdala after a preliminary intraventricular injection of WIN 55.212-2. It was found that WIN 55.212-2 blocked the stimulation-elicited seizures in 80% of tests. A repeated injection of the agonist within 30 days caused an increase in the amplitude of local field potentials and the power of the theta rhythm in all the structures under study. The infusion of kainic acid provoked the onset of status epilepticus in control animals, whereas guinea pigs injected with the agonist (daily, during 25-30 days) did not develop the status. Possible mechanisms of the protective influence of WIN 55.212-2 are discussed.     

Control of flexor motoneuron activity during single leg walking of the stick insect on an electronically controlled treadwheel

In the present study, motoneurons innervating the flexor tibiae muscle of the stick insect (Cuniculina impigra) middle leg were recorded intracellularly while the single leg performed walking-like movements on a treadwheel. Different levels of belt friction (equivalent to a change in load) were used to study the control of activity of flexor motoneurons. During slow leg movements no fast motoneurons were active, but a recruitment of these neurons could be observed during faster leg movements. The firing rate of slow and fast motoneurons increased with incremented belt friction. Also, the force applied to the treadwheel at different frictional levels was adapted closely to the friction of the treadwheel to be overcome. The motoneurons innervating the flexor tibiae were recruited progressively during the stance phase, with the slow motoneurons being active earlier than the fast (half-maximal spike frequency after 10-15% and 50-60% of the stance phase, respectively). The resting membrane potential was more hyperpolarized in fast motoneurons (64.6 +/- 6.5 mV) than in slow motoneurons (-52.9 +/- 5.4 mV). However, the threshold for the initiation of action potentials was not statistically significantly different in both types of flexor motoneurons. Therefore, action potentials were generated in fast motoneurons after a longer period of depolarization and thus later during the stance phase than in slow motoneurons. We show that motoneurons of the flexor tibiae receive substantial common excitatory inputs during the stance phase and that the difference in resting membrane potential between slow and fast motoneurons is likely to play a crucial role in their consecutive recruitment.     

Sensitivity of transformed (phasic to tonic) motor neurons to the neuromodulator 5-HT

Long-term adaptation resulting in a 'tonic-like' state can be induced in phasic motor neurons of the crayfish, Procambarus clarkii, by daily low-frequency stimulation [Lnenicka, G.A., Atwood, H.L., 1985b. Long-term facilitation and long-term adaptation at synapses of a crayfish phasic motoneuron. J. Neurobiol. 16, 97-110]. To test the hypothesis that motor neurons undergoing adaptation show increased responses to the neuromodulator serotonin (5-HT), phasic motor neurons innervating the deep abdominal extensor muscles of crayfish were stimulated at 2.5 Hz, 2 h/day, for 7 days. One day after cessation of conditioning, contralateral control and conditioned motor neurons of the same segment were stimulated at 1 Hz and the induced excitatory post-synaptic potentials (EPSPs) were recorded from DEL(1) muscle fibers innervated by each motor neuron type. Recordings were made in saline without and with 100 nM 5-HT. EPSP amplitudes were increased by 5-HT exposure in all cases. Conditioned muscles exposed to 5-HT showed a 2-fold higher percentage of increase in EPSP amplitude than did control muscles. Thus, the conditioned motor neurons behaved like intrinsically tonic motoneurons in their response to 5-HT. While these results show that long-term adaptation (LTA) extends to 5-HT neuromodulation, no phenotype switch could be detected in the postsynaptic muscle. Protein isoform profiles, including the myosin heavy chains, do not change after 1 week of conditioning their innervating motor neurons.     

The effects of H2O2 on electromechanical activity of the ileum longitudinal muscle

The effects of H2O2 on electrical and mechanical activity of the longitudinal layer from the guinea-pig ileum were studied using sucrose-gap technique and the influence of H2O2 on ionic current was investigated in single smooth muscle cells by the patch-clamp method. In most of the preparations tested, the spontaneous activity observed was composed of slow waves with superimposed action potentials (APs). Both were resistant to tetrodotoxin and atropine. H2O2 (1 mmol/l) evoked sustained 3-5 mV membrane depolarisation, doubled the amplitude of the slow waves and increased their frequency, augmented the APs and reduced their splitting. These changes were accompanied with significant contraction, which had an amplitude comparable to that of the tonic component of 50 mmol/l K+-induced contraction. Calcium-free solution caused membrane depolarisation, reduction of the slow wave amplitude and frequency, disappearance of APs and decreased the mechanical tension of the preparations. Application of H2O2 (1 mmol/l) into the zero-calcium bath solution recovered the APs, which was accompanied by a low amplitude contraction. H2O2 (up to 1 mmol/l) increased the L-type calcium current (I(Ca)) both under conventional whole-cell patch-clamp configuration and under amphotericin-perforated patches by 16 +/- 3%. These data demonstrated that contractile response of the ileum longitudinal smooth muscle preparation evoked by H2O2 was mainly due to the enhanced electrical activity.     

Membrane potential of rat calvaria bone cells: dependence on temperature

The membrane potentials of bone cells derived from calvaria of new born rats was shown to be strongly dependent on temperature. When we lowered the temperature from 36 degrees C to 26 degrees C, cells with spontaneous resting membrane potentials (MP) of -80 to -50 mV depolarized (mean amplitude 8 mV; n = 33), and the membrane resistance increased by approximately 80% (n = 20). The temperature response depended on the actual MP, the reversal potential being in the range of -80 to -90 mV. With the application of ouabain (0.1-1 mmol/liter; n = 12), cells depolarized. Simultaneously, the reversal potential of the temperature response was shifted towards more positive values and approached the actual MP level of the cells. Consequently, the depolarization amplitudes induced by lowering temperature were reduced at spontaneous MP levels. The rise of the membrane resistance during cooling was unaffected. When the extracellular chloride concentration was reduced from 133 to 9 mmol/liter, temperature-dependent depolarizations persisted at spontaneous MP values (n = 5). The findings indicate that the marked effects of temperature changes on the MP of bone-derived cells are mainly determined by changes of the potassium conductance.     

Glutamate potential : differences from the excitatory junctional potential revealed by diltiazem and concanavalin A in crayfish neuromuscular junction.

1. The effect of diltiazem and concanavalin A (Con A) on the crayfish neuromuscular junction was investigated in order to compare the action of L-glutamate with that of the excitatory transmitter. 2. When diltiazem (0.3 nM) was added to the perfusion fluid, the iontophoretic glutamate potential was reduced to about half, whereas the amplitude of excitatory junctional potentials (EJPs) increased by about two times. 3. Dose-response curves of L-glutamate suggested that diltiazem acted in a non-competitive manner. The decrease in amplitude of the glutamate potential caused by diltiazem was not due to the acceleration of desensitization of the glutamate receptor. 4. The increase in amplitude of EJPs caused by diltiazem was due to the increase in membrane resistance. The quantal content and size of extracellular EJPs were not affected by diltiazem. 5. In normal saline, bath application of glutamate decreased the amplitude of both glutamate potentials and EJPs because of desensitization of the glutamate receptor. The decrease in amplitude of the glutamate potential was completely prevented by previous application of Con A (10(-6) M). On the other hand, Con A had no influence on the decrease in amplitude of EJPs. 6. Some possible explanations of these pharmacological differences between glutamate potentials and EJPs revealed by diltiazem and Con A are considered.