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1.
A subpopulation of sensory neurons in the petrosal ganglion transmits information between peripheral chemoreceptors (glomus cells) in the carotid body and relay neurons in the nucleus of the solitary tract. Expression of voltage-gated K+ channels in these neurons was characterized by immunohistochemical localization. Five members of the Kv1 family, Kv1.1, Kv1.2, Kv1.4, Kv1.5 and Kv1.6 and members of two other families, Kv2.1 and Kv4.3, were identified in over 90% of the chemoreceptor neurons. Although the presence of these channel proteins was consistent throughout the population, individual neurons showed considerable variation in K+ current profiles. 相似文献
2.
ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. 总被引:28,自引:0,他引:28
B P Bean 《The Journal of neuroscience》1990,10(1):1-10
The concentration dependence and kinetics of ionic currents activated by extracellular adenosine 5'-triphosphate (ATP) were studied in voltage-clamped dorsal root ganglion neurons from rats and bullfrogs. About 40% of neurons of both species responded to ATP with an increase in membrane conductance. The ATP-activated currents were similar in the 2 species, except that currents in rat neurons desensitized faster. In bullfrog neurons, the conductance was half-maximally activated by about 3 microM ATP; at low concentrations, the conductance increased 3- to 7-fold for a doubling in [ATP], suggesting that several ATP molecules must bind in order to activate the current. A steeper concentration-response relationship than expected from 1:1 binding was also seen in rat neurons. The current activated quickly upon application of ATP and decayed quickly when ATP was removed. Activation kinetics were faster at higher [ATP], with time constants decreasing from about 200 msec at 0.3 microM ATP to about 10 msec at 100 microM ATP. Deactivation kinetics (tau approximately 100-200 msec) were independent of the ATP concentration. The rapid activation and deactivation make it seem likely that the ATP-activated current is mediated by direct ligand binding rather than by a second-messenger system. The experimental observations can be mimicked by a simple model in which ATP must bind to 3 identical, noninteracting sites in order to activate a channel. The potency and kinetics of ATP action were voltage-dependent, with hyperpolarization slowing deactivation and increasing ATP's potency. Deactivation kinetics were also sensitive to the concentration of external Ca, becoming faster in higher Ca. 相似文献
3.
Piao L Lee H Li HY Park CK Cho IH Piao ZG Jung SJ Choi SY Lee SJ Park K Kim JS Oh SB 《Journal of neuroscience research》2006,83(7):1373-1380
We investigated the mechanosensitivity of voltage-gated K+ channel (VGPC) currents by using whole-cell patch clamp recording in rat trigeminal ganglion (TG) neurons. On the basis of biophysical and pharmacological properties, two types of VGPC currents were isolated. One was transient (I(K,A)), the other sustained (I(K,V)). Hypotonic stimulation (200 mOsm) markedly increased both I(K,A) and I(K,V) without affecting their activation and inactivation kinetics. Gadolinium, a well-known blocker of mechanosensitive channels, failed to block the enhancement of I(K,A) and I(K,V) induced by hypotonic stimulation. During hypotonic stimulation, cytochalasin D, an actin-based cytoskeletal disruptor, further increased I(K,A) and I(K,V), whereas phalloidin, an actin-based cytoskeletal stabilizer, reduced I(K,A) and I(K,V). Confocal imaging with Texas red-phalloidin showed that actin-based cytoskeleton was disrupted by hypotonic stimulation, which was similar to the effect of cytochalasin D. Our results suggest that both I(K,A) and I(K,V) are mechanosensitive and that actin-based cytoskeleton is likely to regulate the mechanosensitivity of VGPC currents in TG neurons. 相似文献
4.
Meredith Hay 《Brain research》1998,786(1-2)
Whole-cell and single channel recordings were used to characterize the effects of the immunosuppressant cyclosporine A (CsA) on cardiac sensory neurons (CSN) of the nodose ganglia. Application of 10 nM CsA resulted in a 29.1% decrease in CSN input resistance and an average −8±3 mV hyperpolarization of membrane potential. Application of 10 nM CsA had no effect on evoked Ca++ currents but increased evoked K+ currents by 158.9±24%. Application of 10 nM CsA significantly increased the open probability of KCa channels by 183±9%. These results suggest that application of CsA results in the activation of KCa channels in cardiac sensory neurons and this effect may contribute to the cellular mechanisms underlying CsA modulation of vagal afferent neurons. 相似文献
5.
The physiological role of taurine, an abundant free amino acid in the neural system, is still poorly understood. The aim of this study was to investigate its effect on TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents in enzymatically dissociated neurons from rat dorsal root ganglion (DRG) with conventional whole-cell recording manner under voltage-clamp conditions. A TTX-S Na+ current was recorded preferentially from large DRG neurons and a TTX-R Na+ current preferentially from small ones. For TTX-S Na+ channel, taurine of the concentration > or = 10 mM shifted the activation curve in the depolarizing direction and the inactivation curve in the hyperpolarizing direction. There was no change in the activation curve for TTX-R Na+ channel and the inactivation curve was shifted in the hyperpolarizing direction slightly in the presence of taurine > or = 20 mM. When the recovery kinetics was examined, the presence of taurine resulted in a slower recovery from inactivation of TTX-S currents and no change of TTX-R ones. All the effects of taurine were weakly concentration-dependent and partly recovered quite slowly after washout. Our data indicate that taurine alters the properties of Na+ currents in intact DRG neurons. These may contribute to the understanding of taurine as a natural neuroprotectant and the potential of taurine as a useful medicine for the treatment of sensory neuropathies. 相似文献
6.
Effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of dorsal root ganglion neurons in a neuropathic pain model. 总被引:5,自引:0,他引:5
We hypothesized that abnormal activity and adrenergic sensitivity in injured dorsal root ganglion (DRG) neurons are due to an intrinsic alteration of the cell body membrane. We investigated the effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of DRG neurons in a rat chronic constriction injury (CCI) model. At first, we demonstrated thermal hyperalgesia and sprouting sympathetic nerve fibers in the ipsilateral L4-L5 DRGs. Using whole-cell patch clamp techniques, we found that alpha2-adrenergic stimulus by 10 microM norepinephrine (NE) inhibited inward currents (IBa, Ba2+ as a charge carrier) through voltage-dependent Ca2+ channels (VDCCs) of DRGs in the CCI model by 42%, whereas it enhanced the IBa by 18% in control animals. The inhibitory effect of NE disappeared by pretreatment with the N-type VDCC antagonist omega-conotoxin GVIA (1 microM). NE shifted the inactivation curve to a more negative potential, showing that it has inhibitory effects on IBa both in activated and in inactivated states. alpha2-Adrenergic stimulus also inhibited outward K+ currents by 24% in the CCI model, while it had no effect on the currents in control animals. The inhibitory effect of NE was blocked by pretreatment with the Ca2+-activated K+ (KCa) channel antagonist charybdotoxin (40 nM). The NE-induced inhibitory effects both on N-type VDCC and on KCa channels in injured DRG neurons of the CCI model could lead to cell membrane depolarization, resulting in a spontaneous discharge of action potential and an increase in sensitivity to adrenergic stimulus. 相似文献
7.
Single calcium channels of cultured dorsal root ganglion cells from mouse embryos were studied using patch clamp method in its cell-attached configuration. Two types of activity of unitary calcium channels were found. The first one which arose at membrane potentials near--50-40 mV was characterized by unitary current amplitude of 0.37 +/- 0.04 pA with 40 mmol/l Ca2+ in the pipette solution, mean open time of 0.6 ms and intraburst mean shut time of 1.2 ms. It displayed voltage- and time-dependent inactivation. The corresponding values for the second one which required much more positive depolarization to be activated (approximately 0 mV) and did not express noticeable inactivation were: 0.53 +/- 0.04 pA, 0.8 ms and 0.8 ms. It is concluded that the recorded types of unitary activity are associated respectively with low- and high-threshold calcium currents which have been found earlier while studying whole cell currents. 相似文献
8.
9.
Nociceptive dorsal horn neurones, which are involved in the processing of pain-related information, are inhibited by input from vibration-sensitive, large diameter primary sensory fibres (Wall and Cronly-Dillon, 1960; Salter and Henry, 1990a,b). We have reported previously that the inhibition of spinal nociceptive neurones by vibration is mediated by adenosine acting through P1-purinergic receptors (Salter and Henry, 1987). In a number of different types of cell, adenosine is known to activate K+ currents (Gerber et al., 1989; Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987) and we have recently found that the adenosine-mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP), which is, indeed, caused by a K+ conductance (De Koninck and Henry, 1988, 1992). It has been reported that adenosine-activated K+ channels in cardiac muscle cells are the ATP-sensitive K+ channels (Kirsch et al., 1990). Therefore, we questioned whether these channels might mediate the purinergic IPSP we have observed in nociceptive dorsal horn neurones. We report here that glibenclamide, a blocker of ATP-sensitive K+ channels (Ashcroft, 1988; Schmid Antomarchi et al., 1987a,b), blocks the inhibition of nociceptive neurones by vibratory stimulation when this compound is administered locally by iontophoresis or systemically by intravenous injection. In addition, direct intracellular injection of ATP was found to block the IPSP evoked by vibratory stimulation. These data indicate that the purinergic IPSP in nociceptive spinal neurones is mediated via ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
10.
We investigated the role of large conductance, calcium-activated potassium channels (BK channels) in regulation of the excitability of cerebellar Purkinje neurons. Block of BK channels by iberiotoxin reduced the afterhyperpolarization of spontaneous action potentials in Purkinje neurons in acutely prepared cerebellar slices. To establish the conditions required for activation of BK channels in Purkinje neurons, the dependence of BK channel open probability on calcium concentration and membrane voltage were investigated in excised patches from soma of acutely prepared Purkinje cells. Single channel currents were studied under conditions designed to select for potassium currents and in which voltage-activated currents were largely inactivated. Micromolar calcium concentrations activated channels with a mean single channel conductance of 266 pS. BK channels were activated by both calcium and membrane depolarization, and showed no sign of inactivation. At a given calcium concentration, depolarization over a 60-mV range increased the mean open probability (P(O)) from < 0.1 to > 0.8. Increasing the calcium concentration shifted the voltage required for half maximal activation to more hyperpolarized potentials. The apparent affinity of the channels for calcium increased with depolarization. At -60 mV the apparent affinity was approximately 35 micro m decreasing to approximately 3 micro M at +40 mV. These results suggest that BK channels are unlikely to be activated at resting membrane potentials and calcium concentrations. We tested the hypothesis that Purkinje cell BK channels may be activated by calcium entry during individual action potentials. Significant BK channel activation could be detected when brief action potential-like depolarizations were applied to patches under conditions in which the sole source of calcium was flux across the plasma membrane via the endogenous voltage-gated calcium channels. It is proposed that BK channels regulate the excitability of Purkinje cells by contributing to afterhyperpolarizations and perhaps by shaping individual action potentials. 相似文献
11.
The expression pattern and subcellular distribution of a teleost homologue of the mammalian Kv3.3 potassium channel, AptKv3.3, was examined in the electrosensory lateral line lobe (ELL) and two cerebellar lobes in the hindbrain of the weakly electric gymnotiform Apteronotus leptorhynchus. AptKv3.3 expression was brain specific, with the highest level of expression in the cerebellum and 56% relative expression in the ELL. In situ hybridization revealed that AptKv3.3 mRNA was present in virtually all cell classes in the ELL as well as in the cerebellar lobes eminentia granularis pars posterior (EGp) and corpus cerebellum (CCb). Immunocytochemistry indicated a distribution of AptKv3.3 channels over the entire soma-dendritic axis of ELL pyramidal, granule, and polymorphic cells and over the soma and at least proximal dendrites (100 microm) of multipolar cells and neurons of the ventral molecular layer. AptKv3.3 immunolabel was present at the soma of cerebellar granule, golgi, eurydendroid, and CCb Purkinje cells, with an equally intense label throughout the dendrites of CCb Purkinje cells and EGp eurydendroid cells. Immunolabel was virtually absent in afferent or efferent axon tracts of the ELL but was detected on climbing fiber axons and on the axons and putative terminal boutons of CCb Purkinje cells. These data reveal a prominent soma-dendritic distribution of AptKv3.3 K+ channels in both principal output and local circuit neurons, a pattern that is distinct from the soma-axonal distribution that characterizes all other Kv3 K+ channels examined to date. The widespread distribution of AptKv3.3 immunolabel in electrosensory cells implies an important role in several aspects of signal processing. 相似文献
12.
Aspartate-immunoreactivity (ir) was examined in the mouse trigeminal ganglion (TG). The ir was detected in 34% of TG neurons and their cell bodies were of various sizes (mean +/- S.D. = 1,234 +/- 543 microm(2)). A triple immunofluorescence method revealed the co-expression of aspartate with calcitonin gene-related peptide (CGRP) and parvalbumin; 22% and 14% of aspartate-immunoreactive (ir) neurons were also immunoreactive for CGRP and parvalbumin, respectively. The co-expression of aspartate with both CGRP and parvalbumin was very rare in the TG. By retrograde tracing method, half and 66% of TG neurons which innervate the vibrissa and palate, respectively, contained aspartate-ir. The co-expression of aspartate with CGRP was more common among palatal neurons (36%) compared to vibrissal neurons (22%). Aspartate-ir neurons which co-expressed parvalbumin-ir were numerous in the vibrissa (17%) but not in the palate (4%). These findings may suggest that the function of aspartate-containing TG neurons is correlated with their peripheral receptive fields. 相似文献
13.
14.
Single-channel recordings of three K+-selective currents in cultured chick ciliary ganglion neurons 总被引:3,自引:0,他引:3
P I Gardner 《The Journal of neuroscience》1986,6(7):2106-2116
Multiple distinct K+-selective channels may contribute to action potential repolarization and afterpotential generation in chick ciliary neurons. The channel types are difficult to distinguish by traditional voltage-clamp methods, primarily because of coactivation during depolarization. I have used the extracellular patch-clamp technique to resolve single-channel K+ currents in cultured chick ciliary ganglion (CG) neurons. Three unit currents selective for K+ ions were observed. The channels varied with respect to unit conductance, sensitivity to Ca2+ ions and voltage, and steady-state gating parameters. The first channel, GK1, was characterized by a unit conductance of 14 pico-Siemens (pS) under physiological recording conditions, gating that was relatively independent of membrane potential and intracellular Ca2+ ions, and single-component open-time distributions with time constants of approximately 9 msec. The second channel, GK2, was characterized by a unit conductance of 64 pS under physiological recording conditions and gating that was affected by membrane potential but was not dependent on the activity of intracellular Ca2+ ions. Open-time distributions indicated 2 open states, with open-time constants of 0.09 (61%) and 0.35 (39%) msec, at +40 mV membrane potential. The third channel, GKCa2+, was identified in isolated patch recordings in which the concentration of internal Ca2+ was 10(-7) M or greater, which was an absolute prerequisite for channel opening. GKCa2+ was characterized by a unit conductance of 193 pS in symmetrical 0.15 M KCl solutions, an open-state probability that was a function not only of [Ca2+]i, but also of membrane potential, and single-component open-time distribution with a time constant of 1.11 msec at -10 mV patch potential. These results suggest the presence of at least 3 distinct K+ channel populations in the membrane of cultured chick CG neurons. 相似文献
15.
J Liu M S Evans G J Brewer T J Lee 《Journal of cerebral blood flow and metabolism》2000,20(1):183-191
Results from pharmacological studies have suggested that presynaptic N-type Ca2+ channels play an important role in regulating neuronal Ca2+ influx and transmitter nitric oxide (NO) release in isolated cerebral arteries. However, the presence of N-type Ca2+ channels in cerebral perivascular nerves has not been directly demonstrated. As a major source of cerebral perivascular NOergic innervation is the sphenopalatine ganglion (SPG), adult rat SPGs were cultured and examined by whole-cell patch-clamp technique. One week after growing in the culture medium, significant neurite outgrowth from the SPG neuronal cells was observed. Both soma and neurites of these cells were immunoreactive for N-type Ca2+ channels, transmitter-synthesizing enzymes (choline acetyltransferase and NO synthase), and several neuropeptides (vasoactive intestinal peptide, neuropeptide Y, calcitonin gene-related peptide, substance P, and pituitary adenylate cyclase-activating peptide-38) that had been found in cerebral perivascular nerves in whole-mount vascular preparations. In current-clamp recordings, injection of a small depolarizing current caused action potential firing. In voltage-clamp recordings, the fast inward currents were blocked by tetrodotoxin and outward currents by tetraethylammonium, which is typical for neurons. Most Ca2+ currents isolated by blockade of sodium and potassium currents were blocked by omega-conotoxin, indicating that N-type Ca2+ channels are the dominant voltage-dependent Ca2+ channels regulating Ca2+ influx during membrane depolarization of SPG neurons. The ability to culture postganglionic SPG neurons provides an opportunity to directly study the electrophysiological and pharmacological properties of these neurons. 相似文献
16.
Currents through "fast" (tetrodotoxin-sensitive) sodium channels in rat sensory neurons were measured before and after external application of solutions containing 10 mM Woodward's reagent K (pH 6.0). The membrane treatment has resulted in irreversible changes of stationary activation and inactivation parameters. 相似文献
17.
In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca2+-mediated signaling. In the present review, the A-type K+ (I A) channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca2+ influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of I A channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory. 相似文献
18.
Single calcium channels in isolated dorsal root ganglion cells of the newborn rat were studied using the method of patch clamp in its cell-attached configuration. With 60 mmol/l of Ca2+ in the pipette (extracellular) solution, the amplitude of unitary Ca currents varied from 0.58 +/- 0.05 pA to 0.43 +/- 0.05 pA with a 20 mV change of the potential, which corresponds to a channel conductance of 7 +/- 0.5 pS. The distribution of the open time was monoexponential with the time constant of 0.75 ms not depending on the membrane potential. The distribution of closed time approached a biexponential time course. The fast component (approximately 0.8 ms) showed no dependence on the membrane potential, while the time constant of the slow one decreased with increasing depolarization (from 22 ms to 4 ms with a 20 mV change of the potential). Using experimentally obtained time parameters which describe single calcium channel function and assuming a three-state model of the channel, the numerical values of the rate constants of transitions between individual states were determined. 相似文献
19.
The effects of mercuric chloride and methylmercury chloride on the rat dorsal root ganglion neurons in primary culture were studied by the whole-cell patch clamp technique. gamma-Aminobutyric acid-induced chloride currents were augmented by mercuric chloride in a potent and efficacious manner; at concentrations of 1 and 10 microM, the current amplitude was increased to 130% and 200% of the control. Methylmercury even at 100 microM did not augment but rather decreased the GABA-induced chloride current. Both mercuric chloride and methylmercury generated slow inward currents by themselves. These currents are not mediated by the GABA-activated chloride channels or by voltage-activated sodium, potassium or calcium channels, and are likely to be due to non-specific cation channels. 相似文献
20.