High-voltage-activated calcium currents in basal forebrain neurons during aging

1996 ◽  
Vol 76 (1) ◽  
pp. 158-174 ◽  
Author(s):  
D. Murchison ◽  
W. H. Griffith
Keyword(s):  
Charge Carrier ◽  
High Voltage ◽  
Current Density ◽  
Slow Inactivation ◽  
Peak Current ◽  
Perforated Patch ◽  
Age Related ◽  
Dependent Component ◽  
Voltage Dependent ◽  
Current Densities

1. Both conventional whole cell and perforated-patch voltage-clamp recordings were made of high-voltage-activated (HVA) calcium (Ca2+) channel currents in acutely dissociated medical septum and nucleus of the diagonal band neurons from young (1-3.5 mo) and aged (19-26.5 mo) Fischer 344 rats. Barium (Ba2+) was used as the charge carrier to minimize secondary Ca(2+)-induced conductances and Ca(2+)-induced inactivation. 2. When HVA currents generated by voltage ramps from a holding potential (Vh) of-60 mV were recorded within minutes after whole cell formation, no change in peak current density was observed between young (-44.7 +/- 2.5 pA/pF, mean +/- SE, n = 93) and aged (-44.2 +/- 2.1 pA/pF, n = 86) cells. However, currents recorded later with voltage step protocols revealed a reduction in peak current amplitudes and a trend toward larger peak current densities in aged cells. From a Vh of -60 mV and with steps to -10 mV, current densities were -21.5 +/- 1.9 pA/pF in young cells (n = 55) and -25.0 +/- 2.0 pA/pF in aged cells (n = 44). The differences in current densities recorded by the two protocols were explained by nonspecific current rundown and the development of a slow (min) inactivation process. Slow inactivation was different from conventional rundown of HVA currents because it was reversible with the use of perforated-patch recordings. 3. Perforated-patch recordings were used to characterize slow inactivation. There was significantly less slow inactivation in aged cells. When voltage steps (200 ms in duration, from -80 to -10 mV) were delivered at 12-s intervals, slow inactivation reduced the current after 15 min to 63 +/- 7% of control in young cells and 86 +/- 4% in aged cells (P = 0.028). When voltage steps were delivered at 20-s intervals, the current at the 15th step decreased to 93.4 +/- 1.5% of control in aged cells, compared with 86.6 +/- 1.6% in young (P = 0.007). There was less slow inactivation with increased intervals between voltage steps and with shorter step durations. There was also less inactivation with reduced concentration of charge carrier, indicating a current-dependent component to slow inactivation. Additionally, a voltage-dependent component was evident, because slow inactivation was increased at depolarized VhS. 4. Perforated-patch recordings were used to study at least four pharmacologically distinct fractions of HVA currents in both young and aged cells. Nifedipine (10 microM) blocked 16.9 +/- 2.8% and 23.6 +/- 2.5% of the HVA currents in young and aged cells, respectively. omega-Conotoxin GVIA (500 nM) blocked 53.2 +/- 5.8% in young and 53.6 +/- 2.9% in aged cells. In young cells, omega-agatoxin IVA (200-400 nM) blocked 28.4 +/- 2.2% of the HVA current, and it blocked 29.9 +/- 2.8% in aged cells. A fraction of the current (young cells: 13.8 +/- 2.2%; aged cells: 11.4 +/- 1.6%) was resistant to a combination of all three antagonists. Cadmium (100 microM) completely blocked the remaining HVA current. No significant age-related differences in the HVA current fractions were observed. 5. The HVA current density, current-voltage relationship, and voltage-dependent activation were unchanged with age. However, slow inactivation of HVA currents was reduced in aged cells. The age-related difference in HVA Ca2+ currents reported here suggests a possible mechanism by which Ca2+ homeostasis may be altered in aged neurons.

Investigation of Bipolar Degradation of 1.2 kV BJTs under Different Current and Temperature Conditions

2020 ◽  
Vol 1004 ◽  
pp. 464-471
Author(s):  
Sarah Rugen ◽  
Siddarth Sundaresan ◽  
Ranbir Singh ◽  
Nando Kaminski
Keyword(s):  
Silicon Carbide ◽  
High Voltage ◽  
Current Density ◽  
High Power ◽  
Stacking Faults ◽  
Bipolar Junction Transistors ◽  
Mode Operation ◽  
Different Temperatures ◽  
Current Densities ◽  
The Impact

Bipolar silicon carbide devices are attractive for high power applications offering high voltage devices with low on-state voltages due to plasma flooding. Unfortunately, these devices suffer from bipolar degradation, which causes a significant degradation of the on-state voltage. To explore the generation of stacking faults, which cause the degradation, the impact of the current density and temperature on bipolar degradation is investigated in this work. The analysis is done by stressing the base-collector diode of 1.2 kV bipolar junction transistors (BJTs) as well as the BJTs in common-emitter mode operation with different current densities at different temperatures.

scholarly journals Dravet Variant SCN1AA1783V Impairs Interneuron Firing Predominantly by Altered Channel Activation

2021 ◽  
Vol 15 ◽  
Author(s):  
Nikolas Layer ◽  
Lukas Sonnenberg ◽  
Emilio Pardo González ◽  
Jan Benda ◽  
Ulrike B. S. Hedrich ◽  
...  
Keyword(s):  
Current Density ◽  
Input Resistance ◽  
Epileptic Encephalopathy ◽  
Dravet Syndrome ◽  
Slow Inactivation ◽  
Loss Of Function ◽  
Peak Current Density ◽  
Channel Activation ◽  
Peak Current

Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional NaV1.1 haploinsufficiency in inhibitory interneurons. Recently, a new conditional mouse model expressing the recurrent human p.(Ala1783Val) missense variant has become available. In this study, we provided an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Based on these data, simulated interneuron (IN) firing properties in a conductance-based single-compartment model suggested surprisingly similar firing deficits for NaV1.1A1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired NaV1.1A1783V channel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditional Scn1aA1783V mice. Pan-neuronal activation of the p.Ala1783V in vitro confirmed a predicted IN firing deficit and revealed an accompanying reduction of interneuronal input resistance while demonstrating normal excitability of pyramidal neurons. Altered input resistance was fed back into the model for further refinement. Taken together these data demonstrate that primary loss of function (LOF) gating properties accompanied by altered membrane characteristics may match effects of full haploinsufficiency on the neuronal level despite maintaining physiological peak current density, thereby causing DS.

scholarly journals Short Barriers for Lowering Current-Density in Terahertz Quantum Cascade Lasers

Photonics ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. 7 ◽  
Author(s):  
Liang Gao ◽  
John L. Reno ◽  
Sushil Kumar
Keyword(s):  
Current Density ◽  
Quantum Cascade Lasers ◽  
Longitudinal Optical ◽  
Interface Roughness ◽  
Peak Current ◽  
Quantum Cascade ◽  
Operating Current ◽  
Current Densities ◽  
The Cost ◽  
Cascade Lasers

Scattering due to interface-roughness (IR) and longitudinal-optical (LO) phonons are primary transport mechanisms in terahertz quantum-cascade lasers (QCLs). By choosing GaAs/Al0.10Ga0.90As heterostructures with short-barriers, the effect of IR scattering is mitigated, leading to low operating current-densities. A series of resonant-phonon terahertz QCLs developed over time, achieving some of the lowest threshold and peak current-densities among published terahertz QCLs with maximum operating temperatures above 100 K. The best result is obtained for a three-well 3.1 THz QCL with threshold and peak current-densities of 134 A/cm2 and 208 A/cm2 respectively at 53 K, and a maximum lasing temperature of 135 K. Another three-well QCL designed for broadband bidirectional operation achieved lasing in a combined frequency range of 3.1–3.7 THz operating under both positive and negative polarities, with an operating current-density range of 167–322 A/cm2 at 53 K and maximum lasing temperature of 141 K or 121 K depending on the polarity of the applied bias. By showing results from QCLs developed over a period of time, here we show conclusively that short-barrier terahertz QCLs are effective in achieving low current-density operation at the cost of a reduction in peak temperature performance.

scholarly journals Voltage-gated divalent currents in descending vasa recta pericytes

2010 ◽  
Vol 299 (4) ◽  
pp. F862-F871 ◽  
Author(s):  
Zhong Zhang ◽  
Hai Lin ◽  
Chunhua Cao ◽  
Sandeep Khurana ◽  
Thomas L. Pallone
Keyword(s):  
Charge Carrier ◽  
Charge Carriers ◽  
Slow Inactivation ◽  
Ang Ii ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Vasa Recta ◽  
Maximal Activation ◽  
Voltage Dependent ◽  
Glomerular Arterioles

Multiple voltage-gated Ca2+ channel (CaV) subtypes have been reported to participate in control of the juxtamedullary glomerular arterioles of the kidney. Using the patch-clamp technique, we examined whole cell CaV currents of pericytes that contract descending vasa recta (DVR). The dihydropyridine CaV agonist FPL64176 (FPL) stimulated inward Ca2+ and Ba2+ currents that activated with threshold depolarizations to −40 mV and maximized between −20 and −10 mV. These currents were blocked by nifedipine (1 μM) and Ni2+ (100 and 1,000 μM), exhibited slow inactivation, and conducted Ba2+ > Ca2+ at a ratio of 2.3:1, consistent with “long-lasting” L-type CaV. In FPL, with 1 mM Ca2+ as charge carrier, Boltzmann fits yielded half-maximal activation potential ( V1/2) and slope factors of −57.9 mV and 11.0 for inactivation and −33.3 mV and 4.4 for activation. In the absence of FPL stimulation, higher concentrations of divalent charge carriers were needed to measure basal currents. In 10 mM Ba2+, pericyte CaV currents activated with threshold depolarizations to −30 mV, were blocked by nifedipine, exhibited voltage-dependent block by diltiazem (10 μM), and conducted Ba2+ > Ca2+ at a ratio of ∼2:1. In Ca2+, Boltzmann fits to the data yielded V1/2 and slope factors of −39.6 mV and 10.0 for inactivation and 2.8 mV and 7.7 for activation. In Ba2+, V1/2 and slope factors were −29.2 mV and 9.2 for inactivation and −5.6 mV and 6.1 for activation. Neither calciseptine (10 nM), mibefradil (1 μM), nor ω-agatoxin IVA (20 and 100 nM) blocked basal Ba2+ currents. Calciseptine (10 nM) and mibefradil (1 μM) also failed to reverse ANG II-induced DVR vasoconstriction, although raising mibefradil concentration to 10 μM was partially effective. We conclude that DVR pericytes predominantly express voltage-gated divalent currents that are carried by L-type channels.

Functional alterations in cerebrovascular K+ and Ca2+ channels are comparable between simulated microgravity rat and SHR

2005 ◽  
Vol 289 (3) ◽  
pp. H1265-H1276 ◽  
Author(s):  
Man-Jiang Xie ◽  
Li-Fan Zhang ◽  
Jin Ma ◽  
Hong-Wei Cheng
Keyword(s):  
Current Density ◽  
Cell Voltage ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Cardiovascular Research ◽  
Spontaneously Hypertensive ◽  
Voltage Dependent ◽  
Current Densities ◽  
Wistar Kyoto ◽  
And Control

Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca2+-activated K+ (BKCa), voltage-gated K+ (KV), and L-type voltage-dependent Ca2+ (CaL) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, KV, BKCa, and CaL currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. KV current density decreased in Sus rats vs. Con rats [1.07 ± 0.14 ( n = 22) vs. 1.31 ± 0.28 ( n = 16) pA/pF at +20 mV ( P < 0.05)] and BKCa and CaL current densities increased [BKCa: 1.70 ± 0.37 ( n = 23) vs. 0.88 ± 0.22 ( n = 19) pA/pF at +20 mV ( P < 0.05); CaL: −2.17 ± 0.21 ( n = 35) vs. −1.31 ± 0.10 ( n = 26) pA/pF at +10 mV ( P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: KV current density decreased [1.03 ± 0.33 ( n = 9) vs. 1.62 ± 0.64 ( n = 9) pA/pF at +20 mV ( P < 0.05)] and BKCa and CaL current densities increased [BKCa: 2.54 ± 0.47 ( n = 11) vs. 1.12 ± 0.33 ( n = 12) pA/pF at +20 mV ( P < 0.05); CaL: −3.99 ± 0.53 ( n = 12) vs. −2.28 ± 0.20 ( n = 10) pA/pF at +20 mV ( P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.

Evaluation of T- and L-type Ca2+ currents in shark ventricular myocytes

1995 ◽  
Vol 269 (5) ◽  
pp. H1695-H1703 ◽  
Author(s):  
J. Maylie ◽  
M. Morad
Keyword(s):  
Action Potential ◽  
Time Constant ◽  
Current Density ◽  
Ventricular Myocytes ◽  
Squalus Acanthias ◽  
Na Channel ◽  
Na Current ◽  
Peak Current Density ◽  
Peak Current ◽  
Current Densities

Two types of Ca2+ currents with characteristics of T- and L-type Ca2+ currents were recorded in ventricular myocytes of dogfish (Squalus acanthias). The T-type Ca2+ current activated near -70 mV and had a peak current density of 9.8 pA/pF at -34 mV. The L-type Ca2+ current activated near -50 mV and had a peak current density of 10.6 pA/pF near 0 mV. The threshold for activation of the T-type Ca2+ current was 20 mV negative to that of the tetrodotoxin-sensitive Na+ current. Inactivation of the T-type Ca2+ current was rapid with a limiting time constant of 5 ms at positive potentials. The T-type Ca2+ current was not modulated by isoproterenol or acetylcholine. In dogfish the T-type Ca2+ channel has current densities equivalent to the L-type channel and is likely to activate before the Na+ channel, contributing significantly to generation of the foot of the action potential.

Functional Interaction of Auxiliary Subunits and Synaptic Proteins With CaV1.3 May Impart Hair Cell Ca2+Current Properties

2003 ◽  
Vol 89 (2) ◽  
pp. 1143-1149 ◽  
Author(s):  
Haitao Song ◽  
Liping Nie ◽  
Adrian Rodriguez-Contreras ◽  
Zu-Hang Sheng ◽  
Ebenezer N. Yamoah
Keyword(s):  
Current Density ◽  
Hair Cells ◽  
Synaptic Proteins ◽  
Functional Interaction ◽  
Peak Current Density ◽  
Peak Current ◽  
Hek 293 ◽  
Human Embryonic Kidney Cells ◽  
Auxiliary Subunits ◽  
Voltage Dependent

We assessed the functional determinants of the properties of L-type Ca2+ currents in hair cells by co-expressing the pore-forming CaV1.3α1subunit with the auxiliary subunits β1A and/or α2δ. Because Ca2+channels in hair cells are poised to interact with synaptic proteins, we also co-expressed the CaV1.3α1 subunit with syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome associated protein of 25 kDa (SNAP25). Expression of the CaV1.3α1 subunit in human embryonic kidney cells (HEK 293) produced a dihydropyridine (DHP)-sensitive Ca2+ current (peak current density −2.0 ± 0.2 pA/pF; n = 11). Co-expression with β1A and α2δsubunits enhanced the magnitude of the current (peak current density: CaV1.3α1 + β1A = −4.3 ± 0.8 pA/pF, n = 10; CaV1.3α1 + β1A + α2δ = −4.1 ± 0.6 pA/pF, n = 9) and produced a leftward shift of approximately 9 mV in the voltage-dependent activation of the currents. Furthermore, co-expression of CaV1.3α1 with syntaxin/VAMP/SNAP resulted in at least a twofold increase in the peak current density (−4.7 ± 0.2 pA/pF; n = 11) and reduced the extent of inactivation of the Ca2+currents. Botulinum toxin, an inhibitor of syntaxin, accelerated the inactivation profile of Ca2+ currents in hair cells. Immunocytochemical data also indicated that the Ca2+ channels and syntaxin are co-localized in hair cells, suggesting there is functional interaction of the CaV1.3α1 with auxiliary subunits and synaptic proteins, that may contribute to the distinct properties of the DHP-sensitive channels in hair cells.

scholarly journals Differential regulation of Cav2.2 channel exon 37 variants by alternatively spliced μ-opioid receptors

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Dvij Raval ◽  
Jin Xu ◽  
Ying-Xian Pan ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Current Density ◽  
Kinase Inhibitor ◽  
Splice Variants ◽  
Differential Regulation ◽  
Induced Voltage ◽  
Peak Current Density ◽  
Src Tyrosine Kinase ◽  
Peak Current ◽  
Voltage Dependent

AbstractWe have examined the regulation of mutually exclusive Cav2.2 exon 37a and b variants by the mouse μ-opioid receptor (mMOR) C-terminal splice variants 1, 1C and 1O in tsA-201 cells. Electrophysiological analyses revealed that both channel isoforms exhibit DAMGO-induced voltage-dependent (Gβγ-mediated) inhibition and its recovery by voltage pre-pulses, as well as a voltage-independent component. However, the two channel isoforms differ in their relative extent of voltage-dependent and independent inhibition, with Cav2.2-37b showing significantly more voltage-dependent inhibition upon activation of the three mMOR receptors studied. In addition, coexpression of either mMOR1 or mMOR1C results in an agonist-independent reduction in the peak current density of Cav2.2-37a channels, whereas the peak current density of Cav2.2-37b does not appear to be affected. Interestingly, this decrease is not due to an effect on channel expression at the plasma membrane, as demonstrated by biotinylation experiments. We further examined the mechanism underlying the agonist-independent modulation of Cav2.2-37a by mMOR1C. Incubation of cells with pertussis toxin did not affect the mMOR1C mediated inhibition of Cav2.2-37a currents, indicating a lack of involvement of Gi/o signaling. However, when a Src tyrosine kinase inhibitor was applied, the effect of mMOR1C was lost. Moreover, when we recorded currents using a Cav2.2-37a mutant in which tyrosine 1747 was replaced with phenylalanine (Y1747F), the agonist independent effects of mMOR1C were abolished. Altogether our findings show that Cav2.2-37a and Cav2.2-37b isoforms are subject to differential regulation by C-terminal splice variants of mMORs, and that constitutive mMOR1C activity and downstream tyrosine kinase activity exert a selective inhibition of the Cav2.2-37a splice variant, an N-type channel isoform that is highly enriched in nociceptors. Our study provides new insights into the roles of the MOR full-length C-terminal variants in modulating Cav2.2 channel isoform activities.

scholarly journals Effect of Peak Current Density on Tensile Properties of AZ31B Magnesium Alloy

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1457
Author(s):  
Ichsan Indhiarto ◽  
Tetsuhide Shimizu ◽  
Ming Yang
Keyword(s):  
Magnesium Alloy ◽  
Current Density ◽  
Stress Reduction ◽  
Uniaxial Tensile ◽  
Current Crowding ◽  
Peak Current Density ◽  
Peak Current ◽  
Az31b Magnesium Alloy ◽  
Uniaxial Tensile Testing ◽  
Current Densities

An investigation into the effects, including the athermal effect, of a pulsed current on AZ31B magnesium alloy was carried out. Different peak current densities were applied at the same temperature under uniaxial tensile testing. The results indicate that the stress reduction caused by the increasing peak current density is independent of temperature. The strain hardening coefficient also shows a similar trend. The fracture strain shows the optimum value due to the current crowding effect.

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