scholarly journals Calcium-dependent inactivation of high-threshold calcium currents in human dentate gyrus granule cells

1998 ◽  
Vol 509 (1) ◽  
pp. 39-45 ◽  
Author(s):  
U. Valentin Nägerl ◽  
Istvan Mody
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Calcium Currents ◽  
High Threshold ◽  
Calcium Dependent ◽  
Dependent Inactivation

Ca2+-Dependent Inactivation of High-Threshold Ca2+ Currents in Hippocampal Granule Cells of Patients With Chronic Temporal Lobe Epilepsy

1999 ◽  
Vol 82 (2) ◽  
pp. 946-954 ◽  
Author(s):  
Heinz Beck ◽  
Ralf Steffens ◽  
Uwe Heinemann ◽  
Christian E. Elger
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Feedback Mechanism ◽  
Calcium Currents ◽  
High Threshold ◽  
Kindling Model ◽  
Dependent Inactivation ◽  
Intracellular Ca

Intracellular Ca2+ represents an important trigger for various second-messenger mediated effects. Therefore a stringent control of the intracellular Ca2+ concentration is necessary to avoid excessive activation of Ca2+-dependent processes. Ca2+-dependent inactivation of voltage-dependent calcium currents (VCCs) represents an important negative feedback mechanism to limit the influx of Ca2+ that has been shown to be altered in the kindling model of epilepsy. We therefore investigated the Ca2+-dependent inactivation of high-threshold VCCs in dentate granule cells (DGCs) isolated from the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE) using the patch-clamp method. Ca2+ currents showed pronounced time-dependent inactivation when no extrinsic Ca2+ buffer was present in the patch pipette. In addition, in double-pulse experiments, Ca2+ entry during conditioning prepulses caused a reduction of VCC amplitudes elicited during a subsequent test pulse. Recovery from Ca2+-dependent inactivation was slow and only complete after 1 s. Ca2+-dependent inactivation could be blocked either by using Ba2+ as a charge carrier or by including bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) or EGTA in the intracellular solution. The influence of the cytoskeleton on Ca2+-dependent inactivation was investigated with agents that stabilize and destabilize microfilaments or microtubules, respectively. From these experiments, we conclude that Ca2+-dependent inactivation in human DGCs involves Ca2+-dependent destabilization of both microfilaments and microtubules. In addition, the microtubule-dependent pathway is modulated by the intracellular concentration of GTP, with lower concentrations of guanosine triphosphate (GTP) causing increased Ca2+-dependent inactivation. Under low-GTP conditions, the amount of Ca2+-dependent inactivation was similar to that observed in the kindling model. In summary, Ca2+-dependent inactivation was present in patients with TLE and Ammon’s horn sclerosis (AHS) and is mediated by the cytoskeleton similar to rat pyramidal neurons. The similarity to the kindling model of epilepsy may suggest the possibility of altered Ca2+-dependent inactivation in patients with AHS.

scholarly journals Endogenous intracellular calcium buffering and the activation/inactivation of HVA calcium currents in rat dentate gyrus granule cells.

1991 ◽  
Vol 98 (5) ◽  
pp. 941-967 ◽  
Author(s):  
G Köhr ◽  
I Mody
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Calcium Currents ◽  
High Threshold ◽  
Single Class ◽  
Adult Rat ◽  
Channel Inactivation ◽  
Calbindin D28k ◽  
Kinetics Of ◽  
Ca2 Channels

Granule cells acutely dissociated from the dentate gyrus of adult rat brains displayed a single class of high-threshold, voltage-activated (HVA) Ca2+ channels. The kinetics of whole-cell Ca2+ currents recorded with pipette solutions containing an intracellular ATP regenerating system but devoid of exogenous Ca2+ buffers, were fit best by Hodgkin-Huxley kinetics (m2h), and were indistinguishable from those recorded with the nystatin perforated patch method. In the absence of exogenous Ca2+ buffers, inactivation of HVA Ca2+ channels was a predominantly Ca(2+)-dependent process. The contribution of endogenous Ca2+ buffers to the kinetics of inactivation was investigated by comparing currents recorded from control cells to currents recorded from neurons that have lost a specific Ca(2+)-binding protein, Calbindin-D28K (CaBP), after kindling-induced epilepsy. Kindled neurons devoid of CaBP showed faster rates of both activation and inactivation. Adding an exogenous Ca2+ chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), to the intracellular solution largely eliminated inactivation in both control and kindled neurons. The results are consistent with the hypothesis that endogenous intraneuronal CaBP contributes significantly to submembrane Ca2+ sequestration at a concentration range and time domain that regulate Ca2+ channel inactivation.

Calcium currents of cardiovascular neurons isolated from adult guinea pigs

1987 ◽  
Vol 252 (4) ◽  
pp. H867-H871
Author(s):  
D. L. Kunze
Keyword(s):  
Guinea Pigs ◽  
Action Potentials ◽  
Calcium Current ◽  
Threshold Current ◽  
Bipolar Cells ◽  
Calcium Currents ◽  
High Threshold ◽  
Calcium Dependent ◽  
Low Threshold ◽  
Patch Technique

A preparation of cells isolated from the medial and dorsal nuclei of the solitary tract of the medulla of adult guinea pigs was developed to examine the electrical properties of neurons isolated from an area of the central nervous system which is involved in the control of arterial pressure and heart rate. Bipolar cells of approximately 10 microns diameter were obtained on enzymatic dispersion. The cells were studied with the use of the patch technique for whole cell recording. Action potentials were elicited by depolarizing pulses in the presence of 10(-5) M tetrodotoxin which blocked a sodium-dependent current. These action potentials were calcium dependent and were eliminated by adding 1 mM Cd to the bath. In all cells studied, two voltage-dependent components to the calcium current were identified. In 10 mM Ca a high-threshold component activated at approximately -20 mV from holding potentials of -30 mV. A second lower threshold component was activated at -40 mV from more negative holding potentials of -80 mV. The low-threshold component was rapidly inactivating, whereas the high-threshold current slowly inactivated. The peak amplitudes of the two components were similar. Both components were blocked by 1 mM Cd. A role for the low-threshold calcium current in generating repetitive activity is postulated.

scholarly journals Calcium-dependent inactivation controls cardiac L-type Ca2+ currents under β-adrenergic stimulation

2019 ◽  
Vol 151 (6) ◽  
pp. 786-797 ◽  
Author(s):  
Danna Morales ◽  
Tamara Hermosilla ◽  
Diego Varela
Keyword(s):  
Calcium Current ◽  
Calcium Currents ◽  
Adrenergic Stimulation ◽  
Sodium Calcium Exchanger ◽  
Adrenergic Agonist ◽  
Rat Cardiomyocytes ◽  
Calcium Dependent ◽  
Sodium Calcium ◽  
Dependent Inactivation

The activity of L-type calcium channels is associated with the duration of the plateau phase of the cardiac action potential (AP) and it is controlled by voltage- and calcium-dependent inactivation (VDI and CDI, respectively). During β-adrenergic stimulation, an increase in the L-type current and parallel changes in VDI and CDI are observed during square pulses stimulation; however, how these modifications impact calcium currents during an AP remains controversial. Here, we examined the role of both inactivation processes on the L-type calcium current activity in newborn rat cardiomyocytes in control conditions and after stimulation with the β-adrenergic agonist isoproterenol. Our approach combines a self-AP clamp (sAP-Clamp) with the independent inhibition of VDI or CDI (by overexpressing CaVβ2a or calmodulin mutants, respectively) to directly record the L-type calcium current during the cardiac AP. We find that at room temperature (20–23°C) and in the absence of β-adrenergic stimulation, the L-type current recapitulates the AP kinetics. Furthermore, under our experimental setting, the activity of the sodium–calcium exchanger (NCX) does not affect the shape of the AP. We find that hindering either VDI or CDI prolongs the L-type current and the AP in parallel, suggesting that both inactivation processes modulate the L-type current during the AP. In the presence of isoproterenol, wild-type and VDI-inhibited cardiomyocytes display mismatched L-type calcium current with respect to their AP. In contrast, CDI-impaired cells maintain L-type current with kinetics similar to its AP, demonstrating that calcium-dependent inactivation governs L-type current kinetics during β-adrenergic stimulation.

Respiratory-Like Rhythmic Activity Can Be Produced by an Excitatory Network of Non-Pacemaker Neuron Models

2004 ◽  
Vol 92 (2) ◽  
pp. 686-699 ◽  
Author(s):  
Efstratios K. Kosmidis ◽  
Olivier Pierrefiche ◽  
Jean-François Vibert
Keyword(s):  
Potassium Current ◽  
Potassium Concentration ◽  
Rhythmic Activity ◽  
Calcium Currents ◽  
Oscillatory Activity ◽  
Pacemaker Activity ◽  
High Threshold ◽  
Calcium Dependent ◽  
Network Properties ◽  
External Potassium

It is still unclear whether the respiratory-like rhythm observed in slice preparations containing the pre-Bötzinger complex is of pacemaker or network origin. The rhythm persists in the absence of inhibition, but blocking pacemaker activity did not always result in rhythm abolition. We developed a computational model of the slice to show that respiratory-like rhythm can emerge as a network property without pacemakers or synaptic inhibition. The key currents of our model cell are the low- and high-threshold calcium currents and the calcium-dependent potassium current. Depolarization of a single unit by current steps or by raising the external potassium concentration can induce periodic bursting activity. Gaussian stimulation increased the excitability of the model without evoking oscillatory activity, as indicated by autocorrelation analysis. In response to hyperpolarizing pulses, the model produces prolonged relative refractory periods. At the network level, an increase of external potassium concentration triggers rhythmic activity that can be attributed to cellular periodic bursting, network properties, or both, depending on different parameters. Gaussian stimulation also induces rhythmic activity that depends solely on network properties. In all cases, the calcium-dependent potassium current has a central role in burst termination and interburst duration. However, when periodic inhibition is considered, the activation of this current is responsible for the characteristic amplification ramp of the emerged rhythm. Our results may explain controversial results from studies blocking pacemakers in vitro and show a shift in the role of the calcium-dependent potassium current in the presence of network inhibition.

Characterization of calcium currents in aortic baroreceptor neurons

1992 ◽  
Vol 68 (2) ◽  
pp. 509-517 ◽  
Author(s):  
D. Mendelowitz ◽  
D. L. Kunze
Keyword(s):  
Cell Voltage ◽  
Threshold Current ◽  
Calcium Currents ◽  
Neonatal Rat ◽  
High Threshold ◽  
Aortic Depressor Nerve ◽  
Nodose Ganglia ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Aortic Baroreceptors

1. Calcium currents in identified rat aortic baroreceptors were characterized with the perforated patch whole-cell voltage-clamp technique. Aortic baroreceptors were distinguished from other neurons by the presence of a fluorescent tracer that was previously applied to the aortic depressor nerve. The diversity of calcium currents in unidentified neurons dissociated from neonatal rat nodose ganglia were also examined. 2. A population of aortic baroreceptors (63%, 7 of 11) possessed a low-threshold, also referred to as a T-type, calcium current. This current was typically less than 100 pA in 2 mM Ca [72.7 +/- 20.9 (SE) pA, n = 7], had a rapid activation and inactivation, and inactivated completely at conditioning voltages positive to -50 mV. 3. All aortic baroreceptors possessed high-threshold calcium currents that were activated at voltages positive to -30 mV, with typical maximum amplitudes of 600-1,000 pA (826 +/- 79 pA, n = 11). 4. The high-threshold current inactivated with three exponential rates of decay of tau = 10.7 +/- 2.2 ms, 138 +/- 14.6 ms, and a third tau greater than 3 s. It was not possible to separate the kinetic components of inactivation with conditioning voltages (voltage-dependent inactivation), activation thresholds, deactivation kinetics, or calcium-channel antagonists. 5. The voltage-dependent inactivation of high-threshold calcium currents began at voltages positive to -70 mV and became steeply voltage dependent between -60 and -10 mV. Unexpectedly, the three decay constants were present after all conditioning voltages. There were no conditioning voltages that excluded any component.(ABSTRACT TRUNCATED AT 250 WORDS)

Properties of Voltage-Activated Ca2+ Currents in Acutely Isolated Human Hippocampal Granule Cells

1997 ◽  
Vol 77 (3) ◽  
pp. 1526-1537 ◽  
Author(s):  
H. Beck ◽  
R. Steffens ◽  
U. Heinemann ◽  
C. E. Elger
Keyword(s):  
Steady State ◽  
Granule Cells ◽  
Time Dependent ◽  
High Threshold ◽  
Dentate Granule Cells ◽  
Combined Application ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Animal Models Of Epilepsy ◽  
P Type

Beck, H., R. Steffens, U. Heinemann, and C. E. Elger. Properties of voltage-activated Ca2+ currents in acutely isolated human hippocampal granule cells. J. Neurophysiol. 77: 1526–1537, 1997. Properties of Ba2+ currents through voltage-dependent Ca2+ channels ( I Ba) were investigated in 61 dentate granule cells acutely isolated from the resected hippocampus of nine patients with therapy-refractory temporal lobe epilepsy (TLE). Currents with a high threshold of activation (HVA) peaked at 0 mV, and showed some time-dependent inactivation and a voltage of half-maximal steady-state inactivation ( V 1/2inact) of −16.4 mV. Application of saturating doses of ω-conotoxin (ω-CgTx) GVIA or nifedipine distinguished characteristic N-type (38%) and L-type (62% of HVA currents) Ca2+ currents. Combined application of both agents blocked HVA currents by >95%. In a 10-mo-old child but not in adult patients, an ω-agatoxin IVA (ω-AgaTx IVA)-sensitive but ω-CgTx MVIIC-insensitive, noninactivating component of HVA currents (∼24%) was present that most probably corresponds to a P-type current. A T-type Ca2+ current could be separated from HVA components on the basis of its steady-state voltage-dependent inactivation( V 1/2inact = −71.0 mV). The T-type Ca2+ current isolated by subtraction peaked at more negative potentials (−10 mV), showed a significantly more rapid time-dependent inactivation, and could be selectively blocked by low concentrations of Ni2+. It was insensitive to nifedipine and ω-CgTx GVIA. We conclude that L-, N-, and T-type currents are present in adult human dentate granule cells and an additional P-type current is present in neurons from a 10-mo-old patient. These data may provide a basis for comparison with animal models of epilepsy and for the elucidation of mechanisms of action of drugs intended for use in human disease.

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