P-type Currents Research Articles

Λ b → Λ c form factors from QCD light-cone sum rules* *Supported in part by the National Natural Science Foundation of China (12175218, 11975112); Y.L.S also acknowledges the Natural Science Foundation of Shandong province with (ZR2020MA093); J.G is also supported by the National Natural Science Foundation of China (12147118)

In this study, we calculate the transition form factors of decaying into within the framework of light-cone sum rules with the distribution amplitudes (DAs) of the -baryon. In the hadronic representation of the correlation function, we isolate both the and states so that the form factors can be obtained without ambiguity. We investigate the P-type and A-type currents to interpolate light baryons for comparison because the interpolation current for the baryon state is not unique. We also employ three parametrization models for the DAs of in the numerical calculation. We present the numerical predictions for the form factors and branching fractions, averaged forward-backward asymmetry, averaged final hadron polarization, and averaged lepton polarization of the decays, as well as the ratio of the branching ratios . The predicted is consistent with LHCb data.

A kind of nanofiber-enclosed nanoporous structure prepared through dealloying a Cu-Ti glassy film

A kind of nanofiber-enclosed nanoporous structure is fabricated from a Cu-Ti glassy film by dealloying in an alkaline solution. The Cu-Ti glassy films are prepared by a combination of electron beam evaporation of pure Ti and resistance thermal evaporation of pure Cu. The dealloyed films mainly consist of titanium dioxide and a Cu4Ti3 intermetallic compound. Transient photocurrent response tests show that the obtained nanostructured films have considerable ultraviolet light photoresponse activity and exhibit both the typical n-type and p-type currents under UV-irradiation (wavelength λ = 365 nm). The mechanism is discussed in relation to the special nanostructure of the dealloyed films. The results demonstrate that the dealloyed Cu-Ti glasses have potential for applications in photocurrent detectors.

Unipolar n-Type Black Phosphorus Transistors with Low Work Function Contacts.

Black phosphorus (BP) is a promising two-dimensional (2D) material for nanoscale transistors, due to its expected higher mobility than other 2D semiconductors. While most studies have reported ambipolar BP with a stronger p-type transport, it is important to fabricate both unipolar p- and n-type transistors for low-power digital circuits. Here, we report unipolar n-type BP transistors with low work function Sc and Er contacts, demonstrating a record high n-type current of 200 μA/μm in 6.5 nm thick BP. Intriguingly, the electrical transport of the as-fabricated, capped devices changes from ambipolar to n-type unipolar behavior after a month at room temperature. Transmission electron microscopy analysis of the contact cross-section reveals an intermixing layer consisting of partly oxidized metal at the interface. This intermixing layer results in a low n-type Schottky barrier between Sc and BP, leading to the unipolar behavior of the BP transistor. This unipolar transport with a suppressed p-type current is favorable for digital logic circuits to ensure a lower off-power consumption.

Numerical modeling of ceria-based SOFCs with bi-layer electrolyte free from internal short circuit: Comparison of two cell configurations

A numerical model for ceria-based solid oxide fuel cells (SOFCs) with bi-layer electrolyte is proposed to evaluate the internal short circuit by the comparison of two cell configurations: the electronic barrier electrolyte adjacent to cathode and anode, respectively. In this model, the activation polarization of the electrode reaction and the charge transport of the electrolyte with both n/p-type electronic and oxygen ion conductivity are considered. The activation polarization and the charge transport are described by the Butler-Volmer equation and the Nernst-Planck equation, respectively. Parametric simulations are performed to compare the two bi-layer electrolyte configurations in terms of the open circuit voltage, I–V relationship, leakage current density, power density at 0.7V, oxygen partial pressure distribution and electrochemical efficiency as functions of the temperature and thickness ratio of the electronic barrier electrolyte. From our modeling results, the cell configuration of which the barrier electrolyte is adjacent to cathode has significant p-type leakage current, leading to the lower open circuit voltages and electrochemical efficiency than the other one. The oxygen partial pressure distribution under the open circuit displays the “S” type in the barrier layer, which is related to the change of the n/p-type conductivity of the barrier layer. Besides, the activation polarization greatly influences the open circuit voltage and the oxygen partial pressure distribution between boundaries of electrolytes under open circuit. It is also found that the thickness ratio of the electronic barrier electrolyte can be optimized to maximize the electrochemical performance by balancing the open circuit voltage and ohmic polarization loss.

Large Ca²⁺-dependent facilitation of Ca(V)2.1 channels revealed by Ca²⁺ photo-uncaging.

CaV 2.1 channels constitute a dominant Ca(2+) entry pathway into brain neurons, triggering downstream Ca(2+) -dependent processes such as neurotransmitter release. CaV 2.1 is itself modulated by Ca(2+) , resulting in activity-dependent enhancement of channel opening termed Ca(2+) -dependent facilitation (CDF). Real-time Ca(2+) imaging and Ca(2+) uncaging here reveal that CDF turns out to be strikingly faster, more Ca(2+) sensitive, and larger than anticipated on previous grounds. Robust resolution of the quantitative profile of CDF enables deduction of a realistic biophysical model for this process. These results suggest that CaV 2.1 CDF would figure most prominently in short-term synaptic plasticity and cerebellar Purkinje cell rhythmicity. CaV 2.1 (P-type) voltage-gated Ca(2+) channels constitute a major source of neuronal Ca(2+) current, strongly influencing rhythmicity and triggering neurotransmitter release throughout the central nervous system. Fitting with such stature among Ca(2+) entry pathways, CaV 2.1 is itself feedback regulated by intracellular Ca(2+) , acting through calmodulin to facilitate channel opening. The precise neurophysiological role of this calcium-dependent facilitation (CDF) remains uncertain, however, in large measure because the very magnitude, Ca(2+) dependence and kinetics of CDF have resisted quantification by conventional means. Here, we utilize the photo-uncaging of Ca(2+) with CaV 2.1 channels fluxing Li(+) currents, so that voltage-dependent activation of channel gating is no longer conflated with Ca(2+) entry, and CDF is then driven solely by light-induced increases in Ca(2+) . By using this strategy, we now find that CDF can be unexpectedly large, enhancing currents by as much as twofold at physiological voltages. CDF is steeply Ca(2+) dependent, with a Hill coefficient of approximately two, a half-maximal effect reached by nearly 500nm Ca(2+) , and Ca(2+) on/off kinetics in the order of milliseconds to tens of milliseconds. These properties were established for both native P-type currents in cerebellar Purkinje neurons, as well as their recombinant channel counterparts under heterologous expression. Such features suggest that CDF of CaV 2.1 channels may substantially enhance the regularity of rhythmic firing in cerebellar Purkinje neurons, where regularity is believed crucial for motor coordination. In addition, this degree of extensive CDF would be poised to exert large order-of-magnitude effects on short-term synaptic plasticity via rapid modulation of presynaptic Ca(2+) entry.

Effects of Agonists of μ-Opioid Receptors on P-Type Calcium Channels in Rat Purkinje Neurons

Calcium channels of the P-type play an important role in synaptic transmission in the CNS of mammals; the major part of calcium ions entering the presynaptic terminal comes precisely via these channels. Using the whole-cell patch-clamp technique, we studied the effects of μ-opioids on P-type calcium channels in freshly isolated Purkinje neurons of the rat cerebellum. A selective agonist of μ-opioid receptors, DAMGO (10 nM), caused stable moderate (10 ± 1%, on average) but significant (Р < 0.001; n = 27) potentiation of P-type current in most units. This effect of DAMGO was rather appreciable already at a concentration of 1 nM and reached saturation at 100 nM. The effect developed rapidly (in about 10 sec); it was voltage-dependent and completely reversible. An endogenous selective agonist of μ-opioid receptors, endorphin-1, evoked nearly the same effect (increment 8 ± 1%, n = 6, P < 0.01). DAMGO-caused increase in the amplitude of P-type currents was completely removed after application of an antagonist of opioid receptors, naloxone (100 nM). These data indicate that agonists of μ-opioid receptors, even in nanomolar concentrations, can evoke appreciable potentiation of P-type calcium current mediated by interaction with opioid receptors of the corresponding type.

Compensatory Regulation of Cav2.1 Ca2+Channels in Cerebellar Purkinje Neurons Lacking Parvalbumin and Calbindin D-28k

Ca(v)2.1 channels regulate Ca(2+) signaling and excitability of cerebellar Purkinje neurons. These channels undergo a dual feedback regulation by incoming Ca(2+) ions, Ca(2+)-dependent facilitation and inactivation. Endogenous Ca(2+)-buffering proteins, such as parvalbumin (PV) and calbindin D-28k (CB), are highly expressed in Purkinje neurons and therefore may influence Ca(v)2.1 regulation by Ca(2+). To test this, we compared Ca(v)2.1 properties in dissociated Purkinje neurons from wild-type (WT) mice and those lacking both PV and CB (PV/CB(-/-)). Unexpectedly, P-type currents in WT and PV/CB(-/-) neurons differed in a way that was inconsistent with a role of PV and CB in acute modulation of Ca(2+) feedback to Ca(v)2.1. Ca(v)2.1 currents in PV/CB(-/-) neurons exhibited increased voltage-dependent inactivation, which could be traced to decreased expression of the auxiliary Ca(v)beta(2a) subunit compared with WT neurons. Although Ca(v)2.1 channels are required for normal pacemaking of Purkinje neurons, spontaneous action potentials were not different in WT and PV/CB(-/-) neurons. Increased inactivation due to molecular switching of Ca(v)2.1 beta-subunits may preserve normal activity-dependent Ca(2+) signals in the absence of Ca(2+)-buffering proteins in PV/CB(-/-) Purkinje neurons.

Activation of corticotropin-releasing factor 2 receptor inhibits Purkinje neuron P-type calcium currents via G oα-dependent PKC epsilon pathway

Corticotropin-releasing factor (CRF) receptors have been demonstrated to be widely expressed in the central nervous system and in many peripheral tissues of mammalians. However, it is still unknown whether CRF receptors will function in cerebellar Purkinje neurons. In the present study, we investigated the expression profile of CRF receptors in rat cerebellum and identified a novel functional role of CRFR2 in modulating Purkinje neuron P-type Ca 2+ currents (P-currents). We found that CRFR2α mRNA, but not CRFR1 and CRFR2β, was endogenously expressed in rat cerebellum. Activation of CRFR2 by UCN2 inhibited P-currents in a concentration-dependent manner (IC 50 ~ 0.07 µM). This inhibitory effect was abolished by astressin2B, a CRFR2 antagonist, and was blocked by GDP-β-S, pertussis toxin, or a selective antibody raised against the G oα. Inhibition of phospholipase C (PLC) blocked the inhibitory action of UCN2. The application of diacylglycerol (DAG) antagonist, 1-hexadecyl-2-acetyl-sn-glycerol, as well as inhibition of either protein kinase C or its epsilon isoform (PKCε) abolished the UCN2 effect while 1-oleoyl-2-acetyl-sn-glycerol (EI-150), a membrane-permeable DAG analogue, occluded UCN2-mediated inhibition. In addition, UCN2 significantly increases spontaneous firing frequency of Purkinje neurons in cerebellar slices. In summary, activation of CRFR2 inhibits P-currents in Purkinje neurons via G oα-dependent PLC/PKCε pathway, which might contribute to its physiological functions in the cerebellum.

Complementary multi-gate tunnelling FETs: fabrication, optimisation and application aspects

In this paper fabrication, optimisation and application aspects of complementary Multiple-Gate Tunnelling FETs (MuGTFETs) are presented. Tunnelling FETs (TFETs) are realised in a state-of-the-art low-power multi-gate CMOS technology. n- and p-type tunnelling currents are observed within a single device structure. Digital and analogue device performance is analysed. Measured devices show on-currents in the tens of nA regime, limited by not optimised doping profiles. However, very low leakage currents and promising analogue characteristics are observed. Devices with a channel length of only 65 nm feature an intrinsic gain of more than 300. The scaling potential of multi-gate tunnelling FETs is proven by measurements and device simulations that reveal a low dependence of the device characteristics on the channel length. Extensive device simulations are carried out, indicating that device behaviour can be optimised by gate stack engineering and tuning of the doping profiles. The devices show low temperature dependence and competitive matching behaviour. Based on the well defined temperature behaviour a new voltage reference circuit is proposed as potential application for the MuGTFET.

Causes and Consequences of Oscillations in the Cerebellar Cortex

Cerebellar high-frequency oscillations have been observed for many decades, but their underlying mechanisms have remained enigmatic. In this issue of Neuron, two papers indicate that specific intrinsic mechanisms in the cerebellar cortex contribute to the generation of these oscillations. Middleton et al. show that GABA(A) receptor activation and nonchemical transmission are required for nicotine-dependent oscillations at 30-80 Hz and 80-160 Hz, respectively, while de Solages et al. provide evidence that recurrent inhibition by Purkinje cells is essential for oscillations around 200 Hz.

Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current

The P-type calcium current is mediated by a voltage-sensing CaV2.1 alpha subunit in combination with modulatory auxiliary subunits. In Purkinje neurones, this current has distinctively slow inactivation kinetics that may depend on alternative splicing of the alpha subunit and/or association with different CaVbeta subunits. To better understand the molecular components of P-type calcium current, we cloned a CaV2.1 cDNA from total mouse brain. The full-length CaV2.1 isoform that we isolated (GenBank AY714490) contains sequences recently shown to be present in Purkinje neurones. In agreement with previously published work, the alternatively spliced amino acid V421, implicated in slow inactivation, was not encoded in AY714490 and was absent from reverse transcription-polymerase chain reaction products generated from single Purkinje cells. Next, we studied the expression of the four known mouse auxiliary CaVbeta2 isoforms in Purkinje neurones. Confirmation of the presence of CaVbeta2a in Purkinje cells, previously shown by others to slow CaV2.1 kinetics, led us to characterize its influence on current dynamics. We studied currents generated by the clone AY714490 coexpressed in tsA201 cells with four different CaVbeta subunits. In addition to the well-documented slowing of open-state inactivation kinetics, coexpression with the CaVbeta2a subunit also protected CaV2.1 channels from closed-state inactivation and prevented the channel from inactivating during physiological trains of action potential-like stimuli. This strong resistance to inactivation parallels the property of Purkinje neurone P-type currents and is suggestive of a role for CaVbeta2a in modulating the inactivation properties of P-type calcium currents in Purkinje neurones.

Protease Treatment of Cerebellar Purkinje Cells Renders ω-Agatoxin IVA-Sensitive Ca2+ Channels Insensitive to Inhibition by ω-Conotoxin GVIA

The identification of currents carried by N- and P-type Ca(2+) channels in the nervous system relies on the use of omega-conotoxin (CTx) GVIA and omega-agatoxin (Aga) IVA. The peptide omega-Aga-IVA inhibits P-type currents at nanomolar concentrations and N-type currents at micromolar concentrations. omega-CTx-GVIA blocks N-type currents, but there have been no reports that it can also inhibit P-type currents. To assess the effects of omega-CTx-GVIA on P-type channels, we made patch-clamp recordings from the soma of Purkinje cells in cerebellar slices of mature [postnatal days (P) 40-50, P40-50] and immature (P13-20) rats, in which P-type channels carry most of the Ca(2+) channel current (>/=85%). These showed that micromolar concentrations of omega-CTx-GVIA inhibited the current in P40-50 cells (66%, 3 microM; 78%, 10 microM) and in P13-20 Purkinje cells (86%, 3 muM; 89%, 10 microM). The inhibition appeared to be reversible, in contrast to the known irreversible inhibition of N-type current. Exposure of slices from young animals to the enzyme commonly used to dissociate Purkinje cells, protease XXIII, abolished the inhibition by omega-CTx-GVIA but not by omega-Aga-IVA (84%, 30 nM). Our finding that micromolar concentrations of omega-CTx-GVIA inhibit P-type currents suggests that specific block of N-type current requires the use of submicromolar concentrations. The protease-induced removal of block by omega-CTx-GVIA but not by omega-Aga-IVA indicates a selective proteolytic action at site(s) on P-type channels with which omega-CTx-GVIA interacts. It also suggests that Ca(2+) channel pharmacology in neurons dissociated using protease may not predict that in neurons not exposed to the enzyme.

Imaging of the Schottky Barriers and Charge Depletion in Carbon Nanotube Transistors

The photovoltage produced by local illumination at the Schottky contacts of carbon nanotube field-effect transistors varies substantially with gate voltage. This is particularly pronounced in ambipolar nanotube transistors where the photovoltage switches sign as the device changes from p-type to n-type. The detailed transition through the insulating state can be recorded by mapping the open-circuit photovoltage as a function of excitation position. These photovoltage images show that the band-bending length can grow to many microns when the device is depleted. In our palladium-contacted devices, the Schottky barrier for electrons is much higher than that for holes, explaining the higher p-type current in the transistor. The depletion width is 1.5 mum near the n-type threshold and smaller than our resolution of 400 nm near the p-type threshold. Internal photoemission from the metal contact to the carbon nanotube and thermally assisted tunneling through the Schottky barrier are observed in addition to the photocurrent that is generated inside the carbon nanotube.

Calcium channel subtypes – another layer of complexity to an already intricate story

Calcium channel subtypes – another layer of complexity to an already intricate story

Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons

Endocannabinoids released by postsynaptic cells inhibit neurotransmitter release in many central synapses by activating presynaptic cannabinoid CB1 receptors. In particular, in the cerebellum, endocannabinoids inhibit synaptic transmission at granule cell to Purkinje cell synapses by modulating presynaptic calcium influx via N-, P/Q-, and R-type calcium channels. Using whole cell patch-clamp techniques, we show that in addition to this presynaptic action, both synthetic and endogenous cannabinoids inhibit P-type calcium currents in isolated rat Purkinje neurons independent of CB1 receptor activation. The IC50 for the anandamide (AEA)-induced inhibition of P-current peak amplitude was 1.04 +/- 0.04 microM. In addition, we demonstrate that all the tested cannabinoids in a physiologically relevant range of concentrations strongly accelerate inactivation of P currents. The effects of AEA cannot be attributed to the metabolism of AEA because a nonhydrolyzing analogue of AEA, methanandamide inhibited P-type currents with a similar efficacy. All effects of cannabinoids on P-type Ca2+ currents were insensitive to antagonists of CB1 cannabinoid or vanilloid TRPV1 receptors. In cerebellar slices, WIN 55,212-2 significantly affected spontaneous firing of Purkinje neurons in the presence of CB1 receptor antagonist, in a manner similar to that of a specific P-type channel antagonist, indicating a possible functional implication of the direct effects of cannabinoids on P current. Taken together these findings demonstrate a functionally important direct action of cannabinoids on P-type calcium currents.

Coexpression of Voltage-Dependent Calcium Channels Ca v 1.2, 2.1a, and 2.1b in Vascular Myocytes

Voltage-dependent Ca2+ channels Cav1.2 (L type) and Cav2.1 (P/Q type) are expressed in vascular smooth muscle cells (VSMCs) and are important for the contraction of renal resistance vessels. In the present study we examined whether native renal VSMCs coexpress L-, P-, and Q-type Ca2+ currents. The expression of both Cav2.1a (P-type) and Cav2.1b (Q-type) mRNA was demonstrated by RT-PCR in renal preglomerular vessels from rats and mice. Immunolabeling was performed on A7r5 cells, renal cryosections, and freshly isolated renal VSMCs with anti-Cav1.2 and anti-Cav2.1 antibodies. Conventional and confocal microscopy revealed expression of both channels in all of the smooth muscle cells. Whole-cell patch clamp on single preglomerular VSMCs from mice showed L-, P-, and Q-type currents. Blockade of the L-type currents by calciseptine (20 nmol/L) inhibited 35.6+/-3.9% of the voltage-dependent Ca2+ current, and blocking P-type currents (omega-agatoxin IVA 10 nmol/L) led to 20.2+/-3.0% inhibition, whereas 300 nmol/L of omega agatoxin IVA (blocking P/Q-type) inhibited 45.0+/-7.3%. In rat aortic smooth muscle cells (A7r5), blockade of L-type channels resulted in 28.5+/-6.1% inhibition, simultaneous blockade of L-type and P-type channels inhibited 58.0+/-11.8%, and simultaneous inhibition of L-, P-, and Q-type channels led to blockade (88.7+/-5.6%) of the Ca2+ current. We conclude that aortic and renal preglomerular smooth muscle cells express L-, P-, and Q-type voltage-dependent Ca2+ channels in the rat and mouse.

Developmental Activation of Calmodulin-Dependent Facilitation of Cerebellar P-Type Ca2+Current

P-type (CaV2.1) Ca2+ channels are a central conduit of neuronal Ca2+ entry, so their Ca2+ feedback regulation promises widespread neurobiological impact. Heterologous expression of recombinant CaV2.1 channels demonstrates that the Ca2+ sensor calmodulin can trigger Ca2+-dependent facilitation (CDF) of channel opening. This facilitation occurs when local Ca2+ influx through individual channels selectively activates the C-terminal lobe of calmodulin. In neurons, however, such calmodulin-mediated processes have yet to be detected, and CDF of native P-type current has thus far appeared different, arguably triggered by other Ca2+ sensing molecules. Here, in cerebellar Purkinje somata abundant with prototypic P-type channels, we find that the C-terminal lobe of calmodulin does produce CDF, and such facilitation augments Ca2+ entry during stimulation by repetitive action-potential and complex-spike waveforms. Beyond recapitulating key features of recombinant channels, these neurons exhibit an additional modulatory dimension: developmental upregulation of CDF during postnatal week 2. This phenomenon reflects increasing somatic expression of CaV2.1 splice variants that manifest CDF and progressive dendritic targeting of variants lacking CDF. Calmodulin-triggered facilitation is thus fundamental to native CaV2.1 and rapidly enhanced during early development.

Robustness of Burst Firing in Dissociated Purkinje Neurons with Acute or Long-Term Reductions in Sodium Conductance

Cerebellar Purkinje neurons often generate all-or-none burst firing in response to depolarizing stimuli. Voltage-clamp experiments using action potential waveforms show that burst firing depends on small net inward currents that flow after spikes and reflect the net balance between multiple large currents. Given this, burst firing is surprisingly robust in the face of changes in the magnitude of the underlying currents from cell to cell. We explored the basis of this robustness by examining the effects of reducing the sodium current, the major contributor to the postspike inward current. Burst firing persisted in concentrations of tetrodotoxin that produced half-block of sodium current. This robustness of bursting reflects an acute feedback mechanism whereby waveform changes from the reduced sodium current (reduced spike height and a hyperpolarizing shift in postspike voltage) cause compensatory decreases in postspike potassium currents. In particular, reduced spike height reduces calcium entry and subsequent calcium-activated potassium current, and the hyperpolarizing shift in postspike voltage speeds deactivation of Kv3-like potassium channels. Other experiments examined bursting in Na(v)1.6-/- mice, in which sodium current density is reduced in the long term. Under these circumstances, there was upregulation of both T-type and P-type calcium current and a change in the balance of calcium current and calcium-activated potassium current such that their net influence shifted from being inhibitory during bursts in wild-type neurons to excitatory during bursts from Na(v)1.6-/- mutant neurons. Thus, Purkinje neurons have both acute and long-term feedback mechanisms that serve to maintain burst firing when voltage-dependent sodium conductance is reduced.

Ionic Mechanisms of Burst Firing in Dissociated Purkinje Neurons

Cerebellar Purkinje neurons have intrinsic membrane properties that favor burst firing, seen not only during complex spikes elicited by climbing fiber input but also with direct electrical stimulation of cell bodies. We examined the ionic conductances that underlie all-or-none burst firing elicited in acutely dissociated mouse Purkinje neurons by short depolarizing current injections. Blocking voltage-dependent calcium entry by cadmium or replacement of external calcium by magnesium enhanced burst firing, but it was blocked by cobalt replacement of calcium, probably reflecting block of sodium channels. In voltage-clamp experiments, we used the burst waveform of each cell as a voltage command and used ionic substitutions and pharmacological manipulations to isolate tetrodotoxin (TTX)-sensitive sodium current, P-type and T-type calcium current, hyperpolarization-activated cation current (Ih), voltage-activated potassium current, large-conductance calcium-activated potassium current, and small-conductance calcium-activated potassium (SK) current. Measured near the middle of the first interspike interval, TTX-sensitive sodium current carried the largest inward current, and T-type calcium current was also substantial. Current through P-type channels was large immediately after a spike but decayed rapidly. These inward currents were opposed by substantial components of voltage-dependent and calcium-dependent potassium current. Termination of the burst is caused partly by decay of sodium current, together with a progressive buildup of SK current after the first interspike interval. Although burst firing depends on the net balance between multiple large currents flowing after a spike, it is surprisingly robust, probably reflecting complex interactions between the exact voltage waveform and voltage and calcium dependence of the various currents.

Ethanol withdrawal seizure susceptibility is associated with upregulation of L- and P-type Ca 2+ channel currents in rat inferior colliculus neurons

Calcium currents in the inferior colliculus (IC) are thought to play an important role in ethanol withdrawal hyperexcitability. Here, we report on the modulation of Ca 2+ channel currents in acutely dissociated IC neurons of rats, exhibiting higher incidence of audiogenic seizures when subjected to ethanol withdrawal. Whole cell Ca 2+ channel currents were activated by depolarizing pulses from a holding potential of –90 mV, in 10 mV increments, using barium (Ba 2+) as the charge carrier. The high threshold voltage-activated (HVA) Ca 2+ channel current density increased significantly in IC neurons following ethanol withdrawal. The gating parameters of HVA Ca 2+ channel currents were only slightly altered, while the fraction of current that did not fully inactivate at positive potentials increased significantly following ethanol withdrawal. Pharmacological dissection of HVA Ca 2+ channel currents suggested that the enhanced current, associated with increased incidence of audiogenic seizures following ethanol withdrawal, was carried by L- and P-type Ca 2+ channels. The upregulation of L- and P-type currents may be responsible for IC neuronal hyperexcitability associated with increased susceptibility to ethanol withdrawal seizures.