Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors

The recognition that intracellular free calcium serves as a ubiquitous intracellular signal has motivated efforts to elucidate mechanisms by which cells regulate calcium influx. One route of entry that may offer both spatial and temporal fine resolution for altering calcium levels is that provided by cation-permeable, ligand-gated ion channels. Biophysical measurements as well as calcium imaging techniques demonstrate that neuronal nicotinic acetylcholine receptors as a class have a high relative permeability to calcium; some subtypes equal or exceed all other known receptors in this respect. Activation of nicotinic receptors on neurons can produce substantial increases in intracellular calcium levels by direct passage of calcium through the receptor channel. When multiple classes of nicotinic receptors are expressed by the same neuron, each appears capable of increasing calcium in the cell but may differ with respect to location, temporal response, agonist sensitivity, or regulation in achieving it. As a result, nicotinic receptors must be considered strong candidates for signaling molecules through which neurons regulate a diverse array of cellular events.     

Developmental regulation of plasticity along neurite shafts

Although it is becoming increasingly clear that structural dynamics on neurite shafts play important roles in establishing neuronal architecture, the underlying mechanisms are unknown. The present study investigates local induction of filopodia along the shafts of neurites, a process that, by analogy to the growth cone, can represent the first stage in the generation of a new neuronal process. We show that filopodia can be induced reliably along the neurite shaft in response to a localized electric field stimulus that evokes large local intracellular calcium increases. Neither induction of filopodia nor a local rise in intracellular calcium occurred in calcium free medium. Although calcium induction of neurite filopodia is highly reliable, forming in response to more than 90% of attempts, it is developmental state-dependent, since neurite filopodia could not be induced in neurons previously defined as “stable state.” We have found two distinct changes in stable state neurons that can decrease the ability to induce new neurites. The first is a reduced calcium response: Field stimulation produced large local rises (280 nM) in stable state neurons. Second, stable state neurons change so that even when the stimulus intensity was increased to elicit a calcium response that would have been sufficient to induce filopodia in growing neurites, neurite filopodia were still not induced. Thus, intracellular calcium plays a key role in structural changes along the shafts of neurites. Furthermore, developmental changes in both calcium homeostatic components, and in calcium responsiveness (i.e., the sensitivity of cellular components that modulate neurite morphology) underlie shifts from plasticity to stability of neuronal architecture in this system. © 1995 John Wiley & Sons, Inc.     

Hyperosmotic media inhibit voltage-dependent calcium influx and peptide release in Aplysia neurons

Summary The bag cell neurons of Aplysia provide a model system in which to investigate the effects of hyperosmolality on the electrical and secretory properties of neurons. Brief stimulation of these neurons triggers an afterdischarge of action potentials that lasts approximately 20–30 min, during which time they release several neuroactive peptides. We have found that pre-incubation of intact clusters of bag cell neurons in hyperosmotic media prior to stimulation prevents the initiation of afterdischarges. Furthermore, an increase in osmolality of the external medium during an ongoing afterdischarge causes its premature termination. Hyperosmotic media attenuate the release of peptide evoked by both electrically stimulated afterdischarges and potassium-induced depolarization. The ability of high potassium to depolarize the bag cell neurons is, however, not impaired. Exposure of isolated bag cell neurons to hyperosmotic media also inhibits the amplitude of action potentials evoked by depolarizing current injection and attenuates the voltage-dependent calcium current. In isolated bag cell neurons loaded with the calcium indicator dye, fura-2, hyperosmotic media reduced the rise in intracellular calcium levels that normally occurs in response to depolarization. Our results suggest that the effects of hyperosmotic media on peptide secretion in bag cell neurons can largely be attributed to their effects on calcium entry.This work was supported by NIH Grant NS-18492 to L.K. Kaczmarek.     

Induction of brain-derived neurotrophic factor by convulsant drugs in the rat brain: involvement of region-specific voltage-dependent calcium channels

A high level of hippocampal brain-derived neurotrophic factor (BDNF) in normally aged as compared with young rats suggests that it is important to maintain a considerable level of hippocampal BDNF during aging in order to keep normal hippocampal functions. To elucidate possible mechanisms of endogenous BDNF increase, changes in levels of BDNF were studied in the rat brain following systemic administration of various convulsant agents; excitotoxic glutamate agonists, NMDA, kainic acid and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA); GABA receptor antagonists, picrotoxin, pentylenetetrazole (PTZ) and lindane (gamma-hexachlorocyclohexane); and L-type voltage-dependent calcium channel agonist, BAY-K 8644. Kainic acid and AMPA, but not NMDA, caused remarkable increases in BDNF protein in the rat hippocampus and entorhinal cortex. Picrotoxin, PTZ and lindane stimulated BDNF production in the entorhinal cortex and also in the hippocampus of rats showing very severe convulsions. On the other hand, BAY-K 8644 treatment increased BDNF levels in the neocortex and entorhinal cortex. Maximal levels of BDNF protein were observed at 12--24 h, 8--16 h and 6 h following administration of kainic acid, PTZ and BAY-K 8644, respectively. Kainic acid stimulated BDNF synthesis in presynaptic hippocampal granule neurons, but not in postsynaptic neurons with its receptors, while PTZ and BAY-K 8644 produced the same effects in postsynaptic neurons in the entorhinal cortex (in granule neurons in the hippocampus) and in the whole cortex, respectively. Nifedipine inhibited almost completely BAY-K 8644, but not PTZ, effects. omega-Conotoxin GVIA and DCG-IV partially blocked kainic acid-induced enhancement of BDNF, indicating involvement of L-type and N-type voltage-dependent calcium channels, respectively. In addition, BDNF levels in the hippocampus of mice deficient in D-myo-inositol-1,4,5-triphosphate receptor gene were scarcely different from those in the same region of controls, suggesting little involvement of intracellular calcium increase through this receptor. BAY-K 8644, but not kainic acid or PTZ, stimulated the phosphorylation of cyclic AMP responsive element binding protein. Our results indicate convulsant-dependent stimulation of BDNF production and involvement of region-specific voltage-dependent calcium channels.     

Calcium regulates neuronal differentiation both directly and via co-cultured myocytes

Control of neuronal development by cellular interactions can be regulated by both extracellular and intracellular calcium. Removal of extracellular calcium affects the differentiation of amphibian spinal neurons in vitro by preventing neuronal calcium influx during the production of calcium-dependent action potentials (Holliday and Spitzer, Dev. Biol. 141:13-23, 1990). However, this culture condition affects differentiation through other mechanisms as well. We have investigated the interaction between neurons and myocytes to distinguish direct effects of low extracellular calcium on neuronal differentiation and indirect effects due to interference with neuron-myocyte interactions. We have examined the initiation of neurite outgrowth and the subsequent extension and orientation of processes. We find that (1) the number of neurons that initiate process outgrowth is reduced by the presence of myocytes in a standard medium containing calcium. Experiments with muscle-conditioned medium indicate that the production and/or secretion of inhibitory cues is calcium dependent. (2) When neurite initiation occurs, neuronal architecture in the absence of myocytes is similar to that in their presence, either in standard or in calcium-free medium, although neurite extension is enhanced by the absence of calcium. (3) Conditioned medium (CM) experiments additionally demonstrate that the orientation of neurite outgrowth to myocyte-derived cues is calcium dependent, although the production of directional cues by myocytes is calcium independent. © 1993 John Wiley & Sons, Inc.     

Age-dependent changes in Ca2+ homeostasis in peripheral neurones: implications for changes in function

Calcium ions represent universal second messengers within neuronal cells integrating multiple cellular functions, such as release of neurotransmitters, gene expression, proliferation, excitability, and regulation of cell death or apoptotic pathways. The magnitude, duration and shape of stimulation-evoked intracellular calcium ([Ca2+]i) transients are determined by a complex interplay of mechanisms that modulate stimulation-evoked rises in [Ca2+]i that occur with normal neuronal function. Disruption of any of these mechanisms may have implications for the function and health of peripheral neurones during the aging process. This review focuses on the impact of advancing age on the overall function of peripheral adrenergic neurones and how these changes in function may be linked to age-related changes in modulation of [Ca2+]i regulation. The data in this review suggest that normal aging in peripheral autonomic neurones is a subtle process and does not always result in dramatic deterioration in their function. We present studies that support the idea that in order to maintain cell viability peripheral neurones are able to compensate for an age-related decline in the function of at least one of the neuronal calcium-buffering systems, smooth endoplasmic reticulum calcium ATPases, by increased function of other calcium-buffering systems, namely, the mitochondria and plasmalemma calcium extrusion. Increased mitochondrial calcium uptake may represent a 'weak point' in cellular compensation as this over time may contribute to cell death. In addition, we present more recent studies on [Ca2+]i regulation in the form of the modulation of release of calcium from smooth endoplasmic reticulum calcium stores. These studies suggest that the contribution of the release of calcium from smooth endoplasmic reticulum calcium stores is altered with age through a combination of altered ryanodine receptor levels and modulation of these receptors by neuronal nitric oxide containing neurones.     

Role for calcium in heat shock‐mediated synaptic thermoprotection in Drosophila larvae

Chemical synaptic transmission is the mechanism for fast, excitation‐coupled information transfer between neurons. Previous work in larval Drosophila has shown that transmission at synaptic boutons is protected by heat shock exposure from subsequent thermal stress through pre‐ and postsynaptic modifications. This protective effect has been, at least partially, ascribed to an up‐regulation in the inducible heat shock protein, hsp70. Effects of hsp70 are correlated with changes to intracellular calcium handling, and the dynamics of intracellular calcium regulate synaptic transmission. Consistent with such a relationship, synaptic plasticity increases at locust neuromuscular junctions following heat shock, suggesting an effect of heat shock on residual presynaptic calcium. Intracellular recording from single abdominal muscle fibers of Drosophila larvae showed that prior heat shock imparts thermoprotection by increasing the upper temperature limit for synaptic transmission. Heat shock exposure enhances short‐term synaptic plasticity and increases its thermosensitivity. Increasing extracellular calcium levels eliminates the physiological differences between control and heat shock preparations; excess calcium itself induces thermoprotection at elevated concentrations. These data support the hypothesis that stress‐induced neuroprotection at the nerve terminal acts, at least partially, through an alteration to the physiological effects of residual presynaptic calcium. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 360–371, 2003     

LmxMPK4, a mitogen-activated protein (MAP) kinase homologue essential for promastigotes and amastigotes of <Emphasis Type="Italic">Leishmania mexicana</Emphasis>

Background  

Leishmania parasites undergo profound morphological and biochemical changes while passing through their life cycle. Protein kinases have been shown to be involved in the differentiation from the extracellular flagellated promastigotes to the intracellular "non-flagellated" amastigotes and vice versa. Moreover, these enzymes are likely involved in the regulation of the proliferation of the different life stages.     

Effects of voltage‐gated calcium channel subunit genes on calcium influx in cultured C. elegans mechanosensory neurons

Voltage‐gated calcium channels (VGCCs) serve as a critical link between electrical signaling and diverse cellular processes in neurons. We have exploited recent advances in genetically encoded calcium sensors and in culture techniques to investigate how the VGCC α₁ subunit EGL‐19 and α₂/δ subunit UNC‐36 affect the functional properties of C. elegans mechanosensory neurons. Using the protein‐based optical indicator cameleon, we recorded calcium transients from cultured mechanosensory neurons in response to transient depolarization. We observed that in these cultured cells, calcium transients induced by extracellular potassium were significantly reduced by a reduction‐of‐function mutation in egl‐19 and significantly reduced by L‐type calcium channel inhibitors; thus, a main source of touch neuron calcium transients appeared to be influx of extracellular calcium through L‐type channels. Transients did not depend directly on intracellular calcium stores, although a store‐independent 2‐APB and gadolinium‐sensitive calcium flux was detected. The transients were also significantly reduced by mutations in unc‐36, which encodes the main neuronal α₂/δ subunit in C. elegans. Interestingly, while egl‐19 mutations resulted in similar reductions in calcium influx at all stimulus strengths, unc‐36 mutations preferentially affected responses to smaller depolarizations. These experiments suggest a central role for EGL‐19 and UNC‐36 in excitability and functional activity of the mechanosensory neurons. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

Evidence for a calcium-dependent outward conductance in endocrine cells of the cockroach, Diploptera punctata

Abstract The cell membranes of the corpora allata of the cockroach Diploptera punctata contain voltage-dependent calcium channels. Depolarizing current injection into cells of the corpora allata in the presence of the calcium channel blockers, cadmium, cobalt or verapamil allows the production of multiple action potentials, as does treatment with the intracellular calcium chelator, BAPTA/AM. These results suggest that calcium currents are involved both in decreasing the excitability and in activating an outward current in cells of the corpora allata. Electrophysiological measurements also suggest a concomitant reduction in outward conductance following the multiple action potentials produced in the presence of the channel blockers or BAPTA/ AM. We hypothesize that the calcium current may play an important role in the regulation of intracellular calcium concentration and Juvenile Hormone biosynthesis.     

Autonomous regulation of growth cone filopodia

The fan-shaped array of filopodia is the first site of contact of a neuronal growth cone with molecules encountered during neuronal pathfinding. Filopodia are highly dynamic structures, and the “action radius” of a growth cone is strongly determined by the length and number of its filopodia. Since interactions of filopodia with instructive cues in the vicinity of the growth cone can have effects on growth cone morphology within minutes, it has to be assumed that a large part of the signaling underlying such morphological changes resides locally within the growth cone proper. In this study, we tested the hypothesis that two important growth cone parameters namely, the length and number of its filopodiaare regulated autonomously in the growth cone. We previously demonstrated in identified neurons from the snail Helisoma trivolvis that filopodial length and number are regulated by intracellular calcium. Here, we investigated filopodial dynamics and their regulation by the second-messenger calcium in growth cones which were physically isolated from their parent neuron by neurite transection. Our results show that isolated growth cones have longer but fewer filopodia than growth cones attached to their parent cell. These isolated growth cones, however, are fully capable of undergoing calcium-induced cytoskeletal changes, suggesting that the machinery necessary to perform changes in filopodial length and number is fully intrinsic to the growth cone proper. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 179–192, 1998     

容量性钙内流通道的分子代表

细胞内钙库排空产生一种信号,诱导细胞膜上的钙库操纵的钙通道（SOC）开放,使Ca^2 由细胞外进入细胞内,称为容量性钙内流（CCE）,或钙释放激活的钙通道（CRAC）,可能由果蝇一过性受体电位（trp)和trp样（trpl)基因编码,钙库排空和通道开放之间的偶联机制不清,目前主要提出三种机制：（1）弥散信使;（2）蛋白质－蛋白质之间的相互作用;（3）囊泡分泌。本文综述了CCE的分子代表 ,可能机制及电生理表型。     

Spontaneous calcium transients regulate neuronal plasticity in developing neurons

Calcium ions play critical roles in neuronal differentiation. We have recorded transient, repeated elevations of calcium in embryonic Xenopus spinal neurons over periods of 1 h in vitro and in vivo, confocally imaging fluo 3-loaded cells at 5 s intervals. Calcium spikes and calcium waves are found both in neurons in culture and in the intact spinal cord. Spikes rise rapidly to approximately 400% of baseline fluorescence and have a double exponential decay, whereas waves rise slowly to approximately 200% of baseline fluorescence and decay slowly as well. Imaging of fura 2-loaded neurons indicates that intracellular calcium increases from 50 to 500 nM during spikes. Both spikes and waves are abolished by removal of extracellular calcium. Developmentally, the incidence and frequency of spikes decrease, whereas the incidence and frequency of waves are constant. Spikes are generated by spontaneous calcium-dependent action potentials and also utilize intracellular calcium stores. Waves are produced by a mechanism that does not involve classic voltage-dependent calcium channels. Spikes are required for expression of the transmitter GABA and for potassium channel modulation. Waves in growth cones are likely to regulate neurite extension. The results demonstrate the roles of a novel signaling system in regulating neuronal plasticity, that operates on a time scale 10⁴ times slower than that of action potentials. © 1995 John Wiley & Sons, Inc.     

Copper-induced intracellular calcium release requires extracellular calcium entry and activation of L-type voltage-dependent calcium channels in Ulva compressa

The marine alga Ulva compressa exposed to 10 µM copper showed a triphasic increase of intracellular calcium with maximal levels at 2, 3 and 12 h involving the activation of ryanodine-, Ins(1,4,5)P₃- and NAADP-sensitive calcium channels. In order to analyze the requirement of extracellular calcium entry for intracellular calcium release as well as the activation of voltage-dependent calcium channels (VDCC) and phospholipase C, U. compressa was treated with EGTA, a non-permeable calcium chelating agent, with verapamil, nipfedipine and diltiazem, inhibitors of L-type VDCC, and with neomycin and U731222, inhibitors of phospholipase C. The release of intracellular calcium was partially inhibited with EGTA at 2 and 3 h and completely inhibited at 12 h of copper exposure and decreased with inhibitors of L-type VDCC and phospholipase C. Thus, copper-induced intracellular calcium release depends on calcium entry and activation of L-type VDCC and phospholipase C. An integrative model of copper-induced cellular responses in U. compressa is presented.     

Identification and characterization of a calcium channel gamma subunit expressed in differentiating neurons and myoblasts

Transient elevations of intracellular calcium (calcium transients) play critical roles in many developmental processes, including differentiation. Although the factors that regulate calcium transients are not clearly defined, calcium influx may be controlled by molecules interacting with calcium channels, including channel regulatory subunits. Here, we describe the chick gamma4 regulatory subunit (CACNG4), the first such subunit to be characterized in early development. CACNG4 is expressed early in the cranial neural plate, and later in the cranial and dorsal root ganglia; importantly, the timing of this later expression correlates precisely with the onset of neuronal differentiation. CACNG4 expression is also observed in nonneuronal tissues undergoing differentiation, specifically the myotome and a subpopulation of differentiating myoblasts in the limb bud. Finally, within the distal cranial ganglia, we show that CACNG4 is expressed in placode-derived cells (prospective neurons), but also, surprisingly, in neural crest-derived cells, previously shown to form only glia in this location; contrary to these previous results, we find that neural crest cells can form neurons in the distal ganglia. Given the proposed role of CACNG4 in modulating calcium channels and its expression in differentiating cells, we suggest that CACNG4 may promote differentiation via regulation of intracellular calcium levels.     

Ionic mechanism of a voltage-dependent current elicited by cyclic AMP

Intracellular pressure injection of cyclic AMP induces a slow voltage-dependent inward current in some neurons of Aplysia californica.The time course, voltage dependence, and ionic sensitivities of this response are nearly identical to those of the voltage-dependent calcium current induced by serotonin in the same preparation. The response to cyclic AMP is unaffected by changes in the extracellular concentration of chloride or potassium. The current is slowly but minimally reduced by a sodium-free solution. The calcium channel blocker, cadmium, blocks the current elicited by injection of cyclic AMP. The data presented here suggest that cyclic AMP can induce a voltage-dependent calcium current.     

β-淀粉肽(1-40)对海马神经元高电压激活钙电流的作用及银杏内酯B对该作用的影响

应用全细胞膜片钳技术探讨β-淀粉肽(1-40)(β-amyloid peptide1-40,Aβ1-40)对新鲜分离的大鼠海马CA1区锥体神经元高电压依赖性钙通道电流(high voltage-activated calcium channel current,IHVA)的作用并观察银杏内酯B(ginkgolideB,GB)对该作用的影响.利用细胞外灌流或者电极内液给药的方法,比较加药前后电流幅度的变化以判断药物是否发挥作用.细胞外给予老化处理的Aβ1-40可以浓度依赖性地增强IHVA的幅度,Aβ1-40的浓度为0.01～30 μmol/L时可分别使IHVA幅度增加(5.43±3.01)%(n=8,P＞0.05)、(10.49±4.13)%(n=11,P＞0.05)、(40.69±8.01)%(n=16,P＜0.01)、(58.32±4.85)%(n=12,P＜0.01)和(75.45±5.81)%(n=6,P＜0.01);新鲜配制的Aβ1-40对IHVA几乎没有影响(n=5,P＞0.05).L-型钙通道阻断剂nifedipine可以抵消Aβ1-40对IHVA的增强作用.Aβ1-40(1.0μmol/L)对IHVA的增强作用可以被cAMP的类似物8-Br-cAMP和腺苷酸环化酶(adenylyl cyclase,AC)的激动剂forskolin增强[分别为(66.19±5.74)%,P＜0.05和(73.21±6.90)%,P＜0.05],被蛋白激酶A(protein kinaseA,PKA)的抑制剂H-89减弱[(20.08±2.18)%,P＜0.05].GB可有效地减弱Aβ1-40对IHVA的增强作用.以上结果表明Aβ1-40可通过AC-cAMP-PKA增强IHVA引起胞内钙超载,这可能是其产生神经毒性作用的机制之一.GB可通过抑制Aβ1-40引起的异常钙离子内流对神经元起一定保护作用.     

Cross-Talk between Reactive Oxygen Species and Calcium in Living Cells

The results of many investigations have shown that calcium is essential for production of reactive oxygen species (ROS). Elevation of intracellular calcium level is responsible for activation of ROS-generating enzymes and formation of free radicals by the mitochondria respiratory chain. On the other hand, an increase in intracellular calcium concentration may be stimulated by ROS. H₂O₂ has been recently shown to accelerate the overall channel opening process in voltage-dependent calcium channels in plant and animal cells. The 1,4,5-inositol-triphosphate-receptors as well as the ryanodine receptors of sarcoplasmic reticulum have also been demonstrated to be redox-regulated. Activity of Ca²⁺-ATPases and Na²⁺/Ca²⁺ exchangers of animal cells are modulated by the intracellular redox state. Simultaneously, Ca²⁺ may activate antioxidant enzymes, such as plant catalase and glutathione reductase, and increase the level of superoxide dismutase in animal cells. Reviewed data support the speculation that Ca²⁺ and ROS are two cross-talking messengers in various cellular processes.     

Kynurenate treatment of autaptic hippocampal microcultures affect localized voltage-dependent calcium diffusion in the dendrites

It is not clear how different spatial compartments in the neuron are affected during epileptiform activity. In the present study we have examined the spatial and temporal profiles of depolarization induced changes in the intracellular Ca(2+) concentration in the dendrites of cultured autaptic hippocampal pyramidal neurons rendered epileptic experimentally by treatment with kynurenate (2 mM) and Mg(2+) (11.3 mM) in culture (treated neurons). This was examined with simultaneous somatic patch-pipette recording and Ca(2+) imaging experiments using the Ca(2+) indicator Oregon Green 488 BAPTA-1. Neurons stimulated by depolarization under whole-cell voltage clamp conditions revealed Ca(2+) entry at localized sites in the dendrites. Ca(2+) transients were observed even in the presence of NMDA and AMPA receptor antagonists suggesting that the opening of voltage gated calcium channels primarily triggered the local Ca(2+) changes. Peak Ca(2+) transients in the dendrites of treated neurons were larger compared to the signals recorded from the control neurons. Dendritic Ca(2+) transients in treated neurons showed a distance dependent scaling. Estimation of dendritic local Ca(2+) diffusion coefficients indicated higher values in the treated neurons and a higher availability of free Ca(2+). Simulation studies of Ca(2+) dynamics in these localized dendritic compartments indicate that local Ca(2+) buffering and removal mechanisms may be affected in treated neurons. Our studies indicate that small dendritic compartments are rendered more vulnerable to changes in intracellular Ca(2+) following induction of epileptiform activity. This can have important cellular consequences including local membrane excitability through mechanisms that remain to be elucidated.     

Critical role of intracellular calcium in plasticity mechanisms of defense behavior command neurons LPl1 and PPl1 of Helix lucorum during nociceptive sensitization

The role of intracellular calcium in changes in excitability and responses of defense behavior command neurons LP11 and PP11 of Helix lucorum to sensory stimulation was investigated in semi-intact preparation of a snail during nociceptive sensitization. It was found that application of sensitizing stimuli onto the snail's head initiated membrane depolarization, increase in its excitability as well as depression of neural responses evoked by sensory stimuli in short-term period of sensitization and significant facilitation of neural responses in long-term period of sensitization. To elucidate the contribution of LP11 and PP11 neurons in plasticity rearrangements involved in the mechanisms of sensitization, we applied sensitizing stimuli during strong hyperpolarization of the neurons or after intracellular injection of calcium chelators. Application of sensitizing stimuli during hyperpolarization of the neurons suppressed the increase in membrane excitability and depressed the neural responses evoked by chemical stimulation of snail's head i.m. short- and long-term periods of sensitization. At the same time, synaptic facilitation of neural responses evoked by tactile stimulation of snail's head and foot was observed, which was similar to synaptic facilitation in the control sensitized snail. Intracellular injection of EGTA or BARTA (calcium chelators) before sensitization suppressed synaptic facilitation in neural responses evoked by sensory stimulation. Under these conditions, the increase in excitability was more pronounced then in the control snail neurons. The experimental results suggest the changes in neural responses evoked by sensory stimulation in sensitized snails involve postsynaptic calcium-dependent mechanisms of plasticity in LP11 and PP11 neurons.