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1.
The nucleus accumbens (NAc), a critical structure of the brain reward circuit, is implicated in normal goal-directed behaviour
and learning as well as pathological conditions like schizophrenia and addiction. Its major cellular substrates, the medium
spiny (MS) neurons, possess a wide variety of dendritic active conductances that may modulate the excitatory post synaptic
potentials (EPSPs) and cell excitability. We examine this issue using a biophysically detailed 189-compartment stylized model
of the NAc MS neuron, incorporating all the known active conductances. We find that, of all the active channels, inward rectifying
K + (K IR) channels play the primary role in modulating the resting membrane potential (RMP) and EPSPs in the down-state of the neuron.
Reduction in the conductance of K IR channels evokes facilitatory effects on EPSPs accompanied by rises in local input resistance and membrane time constant.
At depolarized membrane potentials closer to up-state levels, the slowly inactivating A-type potassium channel (K As) conductance also plays a strong role in determining synaptic potential parameters and cell excitability. We discuss the
implications of our results for the regulation of accumbal MS neuron biophysics and synaptic integration by intrinsic factors
and extrinsic agents such as dopamine. 相似文献
2.
K V2.1 is the prominent somatodendritic sustained or delayed rectifier voltage-gated potassium (Kv) channel in mammalian central neurons, and is a target for activity-dependent modulation via calcineurin-dependent dephosphorylation. Using hanatoxin-mediated block of K V2.1 we show that, in cultured rat hippocampal neurons, glutamate stimulation leads to significant hyperpolarizing shifts in the voltage-dependent activation and inactivation gating properties of the K V2.1-component of delayed rectifier K + (IK) currents. In computer models of hippocampal neurons, these glutamate-stimulated shifts in the gating of the K V2.1-component of IK lead to a dramatic suppression of action potential firing frequency. Current-clamp experiments in cultured rat hippocampal neurons showed glutamate-stimulation induced a similar suppression of neuronal firing frequency. Membrane depolarization also resulted in similar hyperpolarizing shifts in the voltage-dependent gating properties of neuronal IK currents, and suppression of neuronal firing. The glutamate-induced effects on neuronal firing were eliminated by hanatoxin, but not by dendrotoxin-K, a blocker of K V1.1-containing channels. These studies together demonstrate a specific contribution of modulation of K V2.1 channels in the activity-dependent regulation of intrinsic neuronal excitability. 相似文献
3.
Activity-dependent regulation of intrinsic excitability has been shown to greatly contribute to the overall plasticity of neuronal circuits. Such neuroadaptations are commonly investigated in patch clamp experiments using current step stimulation and the resulting input-output functions are analyzed to quantify alterations in intrinsic excitability. However, it is rarely addressed, how such changes translate to the function of neurons when they operate under natural synaptic inputs. Still, it is reasonable to expect that a strong correlation and near proportional relationship exist between static firing responses and those evoked by synaptic drive. We challenge this view by performing a high-yield electrophysiological analysis of cultured mouse hippocampal neurons using both standard protocols and simulated synaptic inputs via dynamic clamp. We find that under these conditions the neurons exhibit vastly different firing responses with surprisingly weak correlation between static and dynamic firing intensities. These contrasting responses are regulated by two intrinsic K-currents mediated by Kv1 and K ir channels, respectively. Pharmacological manipulation of the K-currents produces differential regulation of the firing output of neurons. Static firing responses are greatly increased in stuttering type neurons under blocking their Kv1 channels, while the synaptic responses of the same neurons are less affected. Pharmacological blocking of K ir-channels in delayed firing type neurons, on the other hand, exhibit the opposite effects. Our subsequent computational model simulations confirm the findings in the electrophysiological experiments and also show that adaptive changes in the kinetic properties of such currents can even produce paradoxical regulation of the firing output. 相似文献
4.
Upon application of a long-lasting rectangular stimulus, neurons of the substantia gelatinosa ( SG) display three main types of intrinsic firing behavior, tonic, adapting, and delayed onset. The electrical landmark of delayed-firing
neurons (DFNs), i.e., a significant delay before initiation of action potentials (APs), is believed to result from activation
of subthreshold A-type K + current (K A). We checked out this hypothesis by comparing the voltage dependence of the firing delay with steady-state inactivation of
K A in spinal cord slices of 3- to 5-week-old rats. The delay strongly decreased with membrane depolarization and disappeared
at ~ –60 mV; herewith the discharge pattern was transformed to either a tonic or an adapting one. This correlated well with
inactivation of K A recorded in a whole-cell mode in low-Cl – intracellular solution; inactivation was nearly complete at –60 mV (voltage of half-maximum inactivation, V
1/2 ~ –74.5 mV). Unexpectedly, it was found that filling the cells with high-Cl – solution, to minimize the liquid junction potential, produced at least a 10 mV-difference between voltage dependences of
the firing delay and K A inactivation; the latter shifted toward negativity ( V
1/2 ~ –88.3 mV). The results suggest that the K A and its inactivation properties determine the appearance and voltage dependence of the firing delay in SG neurons; the apparent influence of intracellular Cl – on inactivation properties needs further investigation. 相似文献
5.
We have previously shown that late-developing avian nucleus magnocellularis (NM) neurons (embryonic [E] days 19–21) fire action potentials (APs) that resembles a band-pass filter in response to sinusoidal current injections of varying frequencies. NM neurons located in the mid- to high-frequency regions of the nucleus fire preferentially at 75 Hz, but only fire a single onset AP to frequency inputs greater than 200 Hz. Surprisingly, NM neurons do not fire APs to sinusoidal inputs less than 20 Hz regardless of the strength of the current injection. In the present study we evaluated intrinsic mechanisms that prevent AP generation to low frequency inputs. We constructed a computational model to simulate the frequency-firing patterns of NM neurons based on experimental data at both room and near physiologic temperatures. The results from our model confirm that the interaction among low- and high-voltage activated potassium channels (K LVA and K HVA, respectively) and voltage dependent sodium channels (Na V) give rise to the frequency-firing patterns observed in vitro. In particular, we evaluated the regulatory role of K LVA during low frequency sinusoidal stimulation. The model shows that, in response to low frequency stimuli, activation of large K LVA current counterbalances the slow-depolarizing current injection, likely permitting Na V closed-state inactivation and preventing the generation of APs. When the K LVA current density was reduced, the model neuron fired multiple APs per sinusoidal cycle, indicating that K LVA channels regulate low frequency AP firing of NM neurons. This intrinsic property of NM neurons may assist in optimizing response to different rates of synaptic inputs. 相似文献
6.
Apart from their primary function as balance sensors, Hermissenda hair cells are presynaptic neurons involved in the Ca(2+)-dependent neuronal plasticity in postsynaptic B photoreceptors that accompanies classical conditioning. With a view to beginning to understand presynaptic mechanisms of plasticity in the vestibulo-visual system, a locus for conditioning-induced neuronal plasticity, outward currents that may govern the excitability of hair cells were recorded by means of a whole-cell patch-clamp technique. Three K+ currents were characterized: a 4-aminopyridine-sensitive transient outward K+ current (IA), a tetraethyl ammonium-sensitive delayed rectifier K+ current (IK,V), and a Ca(2+)-activated K+ current (IK,Ca). IA activates and decays rapidly; the steady-state activation and inactivation curves of the current reveal a window current close to the apparent resting voltage of the hair cells, suggesting that the current is partially activated at rest. By modulating firing frequency and perhaps damping membrane oscillations, IA may regulate synaptic release at baseline. In contrast, IK,V and IK,Ca have slow onset and exhibit little or no inactivation. These two K+ currents may determine the duration of the repolarization phase of hair-cell action potentials and hence synaptic release via Ca2+ influx through voltage-gated Ca2+ channels. In addition, IK,Ca may be responsible for the afterhyperpolarization of hair cell membrane voltage following prolonged stimulation. 相似文献
7.
Accumulation of amyloid (Aβ) peptides has been suggested to be the primary event in Alzheimer's disease. In neurons, K + channels regulate a number of processes, including setting the resting potential, keeping action potentials short, timing interspike intervals, synaptic plasticity, and cell death. In particular, A‐type K + channels have been implicated in the onset of LTP in mammalian neurons, which is thought to underlie learning and memory. A number of studies have shown that Aβ peptides alter the properties of K + currents in mammalian neurons. We set out to determine the effects of Aβ peptides on the neuronal A‐type K + channels of Drosophila. Treatment of cells for 18 h with 1 μ M Aβ1‐42 altered the kinetics of the A‐type K + current, shifting steady‐state inactivation to more depolarized potentials and increasing the rate of recovery from inactivation. It also caused a decrease in neuronal viability. Thus it seems that alteration in the properties of the A‐type K + current is a prelude to the amyloid‐induced death of neurons. This alteration in the properties of the A‐type K + current may provide a basis for the early memory impairment that was observed prior to neurodegeneration in a recent study of a transgenic Drosophila melanogaster line over‐expressing the human Aβ1‐42 peptide. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献
8.
Barrington's nucleus (BN), commonly known as the pontine micturition center, controls micturition and other visceral functions through projections to the spinal cord. In this study, we developed a rat brain slice preparation to determine the intrinsic and synaptic mechanisms regulating pre‐sympathetic output (PSO) and pre‐parasympathetic output (PPO) neurons in the BN using patch‐clamp recordings. The PSO and PPO neurons were retrogradely labeled by injecting fluorescent tracers into the intermediolateral region of the spinal cord at T13‐L1 and S1‐S2 levels, respectively. There were significantly more PPO than PSO neurons within the BN. The basal activity and membrane potential were significantly lower in PPO than in PSO neurons, and A‐type K + currents were significantly larger in PPO than in PSO neurons. Blocking A‐type K + channels increased the excitability more in PPO than in PSO neurons. Stimulting μ‐opioid receptors inhibited firing in both PPO and PSO neurons. The glutamatergic EPSC frequency was much lower, whereas the glycinergic IPSC frequency was much higher, in PPO than in PSO neurons. Although blocking GABA A receptors increased the excitability of both PSO and PPO neurons, blocking glycine receptors increased the firing activity of PPO neurons only. Furthermore, blocking ionotropic glutamate receptors decreased the excitability of PSO neurons but paradoxically increased the firing activity of PPO neurons by reducing glycinergic input. Our findings indicate that the membrane and synaptic properties of PSO and PPO neurons in the BN are distinctly different. This information improves our understanding of the neural circuitry and central mechanisms regulating the bladder and other visceral organs. 相似文献
9.
In the antennal lobe of the noctuid moth Agrotis ipsilon, most pheromone-sensitive projection neurons (PNs) exhibit a triphasic firing pattern of excitation (E 1)-inhibition (I)-excitation (E 2) in response to a pulse of the sex pheromone. To understand the mechanisms underlying this stereotypical discharge, we developed a biophysical model of a PN receiving inputs from olfactory receptor neurons (ORNs) via nicotinic cholinergic synapses. The ORN is modeled as an inhomogeneous Poisson process whose firing rate is a function of time and is fitted to extracellular data recorded in response to pheromone stimulations at various concentrations and durations. The PN model is based on the Hodgkin-Huxley formalism with realistic ionic currents whose parameters were derived from previous studies. Simulations revealed that the inhibitory phase I can be produced by a SK current (Ca 2+-gated small conductance K + current) and that the excitatory phase E 2 can result from the long-lasting response of the ORNs. Parameter analysis further revealed that the ending time of E 1 depends on some parameters of SK, Ca 2+, nACh and Na + currents; I duration mainly depends on the time constant of intracellular Ca 2+ dynamics, conductance of Ca 2+ currents and some parameters of nACh currents; The mean firing frequency of E 1 and E 2 depends differentially on the interaction of various currents. Thus it is likely that the interplay between PN intrinsic currents and feedforward synaptic currents are sufficient to generate the triphasic firing patterns observed in the noctuid moth A. ipsilon. 相似文献
10.
Moxonidine, an imidazoline deriviatives, suppress the vasopressor sympathetic outflow to produce hypotension. This effect has been known to be mediated in part by suppressing sympathetic outflow via acting imidazoline I 1 receptors (IR 1) at postganglionic sympathetic neurons. But, the cellular mechanism of IR 1-induced inhibition of noradrenaline (NA) release is still unknown. We therefore, investigated the effect of IR 1 activation on voltage-dependent Ca 2+ channels which is known to play an pivotal role in regulating NA in rat superior cervical ganglion (SCG) neurons, using the conventional whole-cell patch-clamp method. In the presence of rauwolscine (3 μΜ), which blocks α 2-adrenoceptor (R α2), moxonidine inhibited voltage-dependent Ca 2+ current ( ICa) by about 30%. This moxonidine-induced inhibition was almost completely prevented by efaroxan (10 μΜ) which blocks IR 1 as well as Rα2. In addition, ω-conotoxin (CgTx) GVIA (1 μΜ) occluded moxonidine-induced inhibition of ICa, but, moxonidine-induced ICa inhibition was not affected by pertussis toxin (PTX) nor shows any characteristics of voltage-dependent inhibition. These data suggest that moxonidine inhibit voltage-dependent N-type Ca 2+ current ( ICa–N) via activating IR 1. Finally, moxonidine significantly decreased the frequency of AP firing in a partially reversible manner. This inhibition of AP firing was almost completely occluded in the presence of ω-CgTx. Taken together, our results suggest that activation of IR 1 in SCG neurons reduced ICa–N in a PTX-and voltage-insensitive pathway, and this inhibition attenuated repetitive AP firing in SCG neurons. 相似文献
11.
BK channels are large conductance potassium channels gated by calcium and voltage. Paradoxically, blocking these channels
has been shown experimentally to increase or decrease the firing rate of neurons, depending on the neural subtype and brain
region. The mechanism for how this current can alter the firing rates of different neurons remains poorly understood. Using
phase-resetting curve (PRC) theory, we determine when BK channels increase or decrease the firing rates in neural models.
The addition of BK currents always decreases the firing rate when the PRC has only a positive region. When the PRC has a negative
region (type II), BK currents can increase the firing rate. The influence of BK channels on firing rate in the presence of
other conductances, such as I
m
and I
h
, as well as with different amplitudes of depolarizing input, were also investigated. These results provide a formal explanation
for the apparently contradictory effects of BK channel antagonists on firing rates. 相似文献
12.
BackgroundRhythmic behaviors, such as walking and breathing, involve the coordinated activity of central pattern generators in the CNS, sensory feedback from the PNS, to motoneuron output to muscles. Unraveling the intrinsic electrical properties of these cellular components is essential to understanding this coordinated activity. Here, we examine the significance of the transient A-type K + current (I A), encoded by the highly conserved Shal/Kv4 gene, in neuronal firing patterns and repetitive behaviors. While I A is present in nearly all neurons across species, elimination of I A has been complicated in mammals because of multiple genes underlying I A, and/or electrical remodeling that occurs in response to affecting one gene. Methodology/Principal FindingsIn Drosophila, the single Shal/Kv4 gene encodes the predominant I A current in many neuronal cell bodies. Using a transgenically expressed dominant-negative subunit (DNK v4), we show that I A is completely eliminated from cell bodies, with no effect on other currents. Most notably, DNK v4 neurons display multiple defects during prolonged stimuli. DNK v4 neurons display shortened latency to firing, a lower threshold for repetitive firing, and a progressive decrement in AP amplitude to an adapted state. We record from identified motoneurons and show that Shal/K v4 channels are similarly required for maintaining excitability during repetitive firing. We then examine larval crawling, and adult climbing and grooming, all behaviors that rely on repetitive firing. We show that all are defective in the absence of Shal/K v4 function. Further, knock-out of Shal/K v4 function specifically in motoneurons significantly affects the locomotion behaviors tested. Conclusions/SignificanceBased on our results, Shal/K v4 channels regulate the initiation of firing, enable neurons to continuously fire throughout a prolonged stimulus, and also influence firing frequency. This study shows that Shal/K v4 channels play a key role in repetitively firing neurons during prolonged input/output, and suggests that their function and regulation are important for rhythmic behaviors. 相似文献
13.
In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K + channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K + channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K + current (I KV). Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that I KV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K + currents. Forskolin inhibited Kv2.1 currents and I KV with an IC 50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels. 相似文献
14.
In a previous paper we described the actions of beta-amyloid on an A-type K + current from Drosophila 3 rd Instar larval neurons. The results were a depolarizing shift in the steady-state voltage dependence of inactivation and an increase in the rate of recovery from inactivation of the current. In this work we have used the simulation program NEURON to construct a model cell. We then use the model to predict the effects of changing the A-type K + current as was observed in the amyloid treated neurons on the firing properties of the cell. We show that changing the steady-state voltage dependence of inactivation of the current to a more depolarized level as observed in experiments in beta-amyloid treated neurons causes an increase in the threshold for the initiation of repetitive firing. However, increasing the rate of recovery from inactivation had no effect. Changing both properties simultaneously had no additional effect over changing the voltage dependence of inactivation alone. Thus, a change in the steady-state properties of the A-type K + current as seen in the amyloid-treated Drosophila cholinergic neurons is sufficient to alter the firing properties of the modeled cell. 相似文献
15.
Recent experimental and theoretical studies have found that active dendritic ionic currents can compensate for the effects of electrotonic attenuation. In particular, temporal summation, the percentage increase in peak somatic voltage responses invoked by a synaptic input train, is independent of location of the synaptic input in hippocampal CA1 pyramidal neurons under normal conditions. This independence, known as normalization of temporal summation, is destroyed when the hyperpolarization-activated current, I
h, is blocked [Magee JC (1999a), Nature Neurosci. 2: 508–514]. Using a compartmental model derived from morphological recordings of hippocampal CA1 pyramidal neurons, we examined the hypothesis that I
h was primarily responsible for normalization of temporal summation. We concluded that this hypothesis was incomplete. With a model that included I
h, the persistent Na + current ( I
NaP), and the transient A-type K + current ( I
A), however, we observed normalization of temporal summation across a wide range of synaptic input frequencies, in keeping with experimental observations. 相似文献
16.
Potassium inward rectifier K IR2.1 channels contribute to the stable resting membrane potential in a variety of muscle and neuronal cell-types. Mutations in the K IR2.1 gene KCNJ2 have been associated with human disease, such as cardiac arrhythmias and periodic paralysis. Crystal structure and homology modelling of K IR2.1 channels combined with functional current measurements provided valuable insights in mechanisms underlying channel function. K IR2.1 channels have been cloned and analyzed from all main vertebrate phyla, except reptilians. To address this lacuna, we set out to clone reptilian K IR2.1 channels. Using a degenerated primer set we cloned the KCNJ2 coding regions from muscle tissue of turtle, snake, bear, quail and bream, and compared their deduced amino acid sequences with those of K IR2.1 sequences from 26 different animal species obtained from Genbank. Furthermore, expression constructs were prepared for functional electrophysiological studies of ectopically expressed K IR2.1 ion channels. In general, KCNJ2 gene evolution followed normal phylogenetic patterns, however turtle K IR2.1 ion channel sequence is more homologues to avians than to snake. Alignment of all 31 K IR2.1 sequences showed that all disease causing K IR2.1 mutations, except V93I, V123G and N318S, are fully conserved. Homology models were built to provide structural insights into species specific amino acid substitutions. Snake K IR2.1 channels became expressed at the plasmamembrane and produced typical barium sensitive (IC 50 ∼6 μM) inward rectifier currents. 相似文献
17.
How the cerebellum carries out its functions is not clear, even for its established roles in motor control. In particular, little is known about how the cerebellar nuclei (CN) integrate their synaptic and neuromodulatory inputs to generate cerebellar output. CN neurons receive inhibitory inputs from Purkinje cells, excitatory inputs from mossy fibre and climbing fibre collaterals, as well as a variety of neuromodulatory inputs, including cholinergic inputs. In this study we tested how activation of acetylcholine receptors modulated firing rate, intrinsic properties and synaptic transmission in the CN. Using in vitro whole-cell patch clamp recordings from neurons in the interpositus nucleus, the acetylcholine receptor agonist carbachol was shown to induce a short-term increase in firing rate, increase holding current and decrease input resistance of interpositus CN neurons. Carbachol also induced long-term depression of evoked inhibitory postsynaptic currents and a short-term depression of evoked excitatory postsynaptic currents. All effects were shown to be dependent upon muscarinic acetylcholine receptor activation. Overall, the present study has identified muscarinic receptor activation as a modulator of CN activity. 相似文献
18.
The effects of sodium metabisulfite (SMB), a general food preservative, on potassium currents in rat dorsal root ganglion
(DRG) neurons were investigated using the whole-cell patch-clamp technique. SMB increased the amplitudes of both transient
outward potassium currents and delayed rectifier potassium current in concentration- and voltage-dependent manner. The transient
outward potassium currents (TOCs) include a fast inactivating (A-current or I
A) current and a slow inactivating (D-current or I
D) current. SMB majorly increased I A, and I D was little affected. SMB did not affect the activation process of transient outward currents (TOCs), but the inactivation
curve of TOCs was shifted to more positive potentials. The inactivation time constants of TOCs were also increased by SMB.
For delayed rectifier potassium current ( I
K), SMB shifted the activation curve to hyperpolarizing direction. SMB differently affected TOCs and I
K, its effects major on A-type K + channels, which play a role in adjusting pain sensitivity in response to peripheral redox conditions. SMB did not increase
TOCs and I
K when adding DTT in pipette solution. These results suggested that SMB might oxidize potassium channels, which relate to adjusting
pain sensitivity in pain-sensing DRG neurons. 相似文献
19.
为了研究杀虫剂等对蜜蜂毒性作用的神经机制,需在体外建立成年蜜蜂脑神经细胞的分离培养和电生理记录技术并研究其正常电生理特征,而对成年蜜蜂脑神经细胞的分离培养和电生理特性的研究报道甚少。我们采用酶解和机械吹打相结合的方法获得了数量较多且活力较好的成年意大利蜜蜂 Apis mellifera脑神经细胞,并用全细胞膜片钳技术研究了成年意大利蜜蜂脑神经细胞对电流和电压刺激的反应,获得了成年意蜂脑神经细胞的基本电生理特征以及钠电流和钾电流的特性。全细胞电流钳的记录结果表明,在体外培养条件下,细胞无自发放电发生,注射电流后仅引起细胞单次放电,引起细胞放电的阈电流平均为60.8±63 pA; 细胞动作电位产生的阈电位平均为−27.4±2.3 mV。用全细胞电压钳记录了神经细胞的钠电流和钾电流。钠电流的分离是在电压刺激下通过阻断钾通道和钙通道实现。细胞的内向钠电流在指令电压为−40~−30 mV左右激活,−10 mV达峰值,钠通道的稳态失活电压V 1/2为−58.4 mV; 外向钾电流成份至少包括较小的快速失活钾电流和和较大的缓慢失活钾电流(占总钾电流的80%),其半激活膜电位V 1/2为3.86 mV,无明显的稳态失活。结果提示缓慢失活钾电流的特征可能是细胞单次放电的机制之一。 相似文献
20.
The properties of slowly inactivating delayed-rectifier K + current ( IKdr) were investigated in NG108-15 neuronal cells differentiated with long-term exposure to dibutyryl cyclic AMP. Slowly inactivating IKdr could be elicited by prolonged depolarizations from −50 to +50 mV. These outward K + currents were found to decay at potentials above −20 mV, and the decay became faster with greater depolarization. Cell exposure to aconitine resulted in the reduction of IKdr amplitude along with an accelerated decay of current inactivation. Under current-clamp recordings, a delay in the initiation of action potentials (APs) in response to prolonged current stimuli was observed in these cells. Application of aconitine shortened the AP initiation in combination with an increase in both width of spike discharge and firing frequency. The computer model, in which state-dependent inactivation of IKdr was incorporated, was also implemented to predict the firing behavior present in NG108-15 cells. As the inactivation rate constant of IKdr was elevated, the firing frequency was progressively increased along with a shortening of the latency for AP appearance. Our theoretical work and the experimental results led us to propose a pivotal role of slowly inactivating IKdr in delayed firing of APs in NG108-15 cells. The results also suggest that aconitine modulation of IKdr gating is an important molecular mechanism through which it can contribute to neuronal firing. 相似文献
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