Fast Calcium-Dependent Inactivation of Calcium Release-Activated Calcium Current (CRAC) in RBL-1 Cells

1999 ◽  
Vol 168 (1) ◽  
pp. 9-17 ◽  
Author(s):  
L. Fierro ◽  
A.B. Parekh
Keyword(s):  
Calcium Current ◽  
Calcium Release ◽  
Calcium Dependent ◽  
Dependent Inactivation

Evidences for calcium-dependent inactivation of calcium current at the frog motor nerve terminal

2006 ◽  
Vol 69 (6) ◽  
pp. 652-655 ◽  
Author(s):  
Marat A. Mukhamedyarov ◽  
Sergey N. Grishin ◽  
Andrey L. Zefirov ◽  
András Palotás
Keyword(s):  
Nerve Terminal ◽  
Calcium Current ◽  
Motor Nerve ◽  
Motor Nerve Terminal ◽  
Calcium Dependent ◽  
Dependent Inactivation

scholarly journals Calcium-dependent inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells.

1988 ◽  
Vol 92 (4) ◽  
pp. 531-548 ◽  
Author(s):  
D Kalman ◽  
P H O'Lague ◽  
C Erxleben ◽  
D L Armstrong
Keyword(s):  
Calcium Channels ◽  
Calcium Current ◽  
State Level ◽  
Gh3 Cells ◽  
Free Calcium ◽  
Pipette Solution ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Exogenous Calcium ◽  
Free Membrane

The inactivation of calcium channels in mammalian pituitary tumor cells (GH3) was studied with patch electrodes under voltage clamp in cell-free membrane patches and in dialyzed cells. The calcium current elicited by depolarization from a holding potential of -40 mV passed predominantly through one class of channels previously shown to be modulated by dihydropyridines and cAMP-dependent phosphorylation (Armstrong and Eckert, 1987). When exogenous calcium buffers were omitted from the pipette solution, the macroscopic calcium current through those channels inactivated with a half time of approximately 10 ms to a steady state level 40-75% smaller than the peak. Inactivation was also measured as the reduction in peak current during a test pulse that closely followed a prepulse. Inactivation was largely reduced or eliminated by (a) buffering free calcium in the pipette solution to less than 10(-8) M; (b) replacing extracellular calcium with barium; (c) increasing the prepulse voltage from +10 to +60 mV; or (d) increasing the intracellular concentration of cAMP, either 'directly' with dibutyryl-cAMP or indirectly by activating adenylate cyclase with forskolin or vasoactive intestinal peptide. Thus, inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells only occurs when membrane depolarization leads to calcium ion entry and intracellular accumulation.

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.

Electrical Properties of a Cockroach Motor Neuron Soma Depend on Different Characteristics of Individual Ca Components

1997 ◽  
Vol 78 (5) ◽  
pp. 2455-2466 ◽  
Author(s):  
Janette D. Mills ◽  
Robert M. Pitman
Keyword(s):  
Electrical Properties ◽  
Motor Neuron ◽  
Action Potentials ◽  
Calcium Current ◽  
Plateau Potentials ◽  
Inward Current ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Different Characteristics ◽  
Neuron Soma

Mills, Janette D. and Robert M. Pitman. Electrical properties of a cockroach motor neuron soma depend on different characteristics of individual Ca components. J. Neurophysiol. 78: 2455–2466, 1997. The “fast” coxal depressor motor neuron (Df) of the cockroach is among the most extensively studied of insect neurons. It has been shown that the cell body of this neuron can exhibit active electrical properties, which may change over time or with chemical modulation. To further understand these electrical events and their modulation, inward currents in Df have been characterized under conditions in which outward currents have been suppressed. The inward current activated at potentials positive to −60 mV and peaked between −10 and 0 mV when measured in barium saline and between 0 and +10 mV when measured in calcium saline. The inward current was insensitive to Ni2+ (100 μM) but reduced by verapamil (50 μM) and abolished by Cd2+ (1 mM). Two components of I Ca were identified by their sensitivity to either 50 μM nifedipine or micromolar Cd2+. The nifedipine-sensitive component activated positive to −60 mV and peaked between −10 and 0 mV, whereas the Cd2+-sensitive component activated positive to −40 mV and peaked between +10 and +20 mV. Immediately after dissection, depolarization of Df evoked plateau potentials, whereas 1–4 h after dissection, depolarization evoked action potentials. The plateau potentials were insensitive to 100 μM Cd2+ but blocked by 50 μM nifedipine, whereas the spikes required a combination of nifedipine (50 μM) and Cd2+ (100 μM) for complete suppression, indicating that only one component of I Ca contributes to the plateau potential, whereas both components contribute to action potentials. Currents measured in calcium saline decayed faster than currents measured in barium saline. The inactivation characteristics were investigated with the use of double-pulse voltage-clamp experiments. I Ca showed a greater degree of inactivation and slower recovery from inactivation than did I Ba. Current decay and the extent of inactivation were reduced after injection of the calcium-chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid (BAPTA). This suggests that the calcium current of this neuron displays calcium-dependent inactivation. An additional mechanism, most probably voltage-dependent inactivation, also occurs because I Ba, even in neurons injected with BAPTA, displayed some inactivation. The inactivation characteristics may be important in determining activity displayed by Df. Indirect evidence suggests that intracellular calcium is high immediately after dissection. At this time, the calcium current may therefore be reduced due to calcium-dependent inactivation. This may, at least partly, explain why the cell does not spike shortly after dissection.

scholarly journals L-type channel inactivation balances the increased peak calcium current due to absence of Rad in cardiomyocytes

2021 ◽  
Vol 153 (9) ◽  
Author(s):  
Brooke M. Ahern ◽  
Andrea Sebastian ◽  
Bryana M. Levitan ◽  
Jensen Goh ◽  
Douglas A. Andres ◽  
...  
Keyword(s):  
Calcium Current ◽  
Knockout Mouse ◽  
Heart Function ◽  
Systolic Function ◽  
Cardiac Contraction ◽  
Calcium Flux ◽  
Double Knockout ◽  
Calcium Dependent ◽  
Dependent Inactivation

The L-type Ca2+ channel (LTCC) provides trigger calcium to initiate cardiac contraction in a graded fashion that is regulated by L-type calcium current (ICa,L) amplitude and kinetics. Inactivation of LTCC is controlled to fine-tune calcium flux and is governed by voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). Rad is a monomeric G protein that regulates ICa,L and has recently been shown to be critical to β-adrenergic receptor (β-AR) modulation of ICa,L. Our previous work showed that cardiomyocyte-specific Rad knockout (cRadKO) resulted in elevated systolic function, underpinned by an increase in peak ICa,L, but without pathological remodeling. Here, we sought to test whether Rad-depleted LTCC contributes to the fight-or-flight response independently of β-AR function, resulting in ICa,L kinetic modifications to homeostatically balance cardiomyocyte function. We recorded whole-cell ICa,L from ventricular cardiomyocytes from inducible cRadKO and control (CTRL) mice. The kinetics of ICa,L stimulated with isoproterenol in CTRL cardiomyocytes were indistinguishable from those of unstimulated cRadKO cardiomyocytes. CDI and VDI are both enhanced in cRadKO cardiomyocytes without differences in action potential duration or QT interval. To confirm that Rad loss modulates LTCC independently of β-AR stimulation, we crossed a β1,β2-AR double-knockout mouse with cRadKO, resulting in a Rad-inducible triple-knockout mouse. Deletion of Rad in cardiomyocytes that do not express β1,β2-AR still yielded modulated ICa,L and elevated basal heart function. Thus, in the absence of Rad, increased Ca2+ influx is homeostatically balanced by accelerated CDI and VDI. Our results indicate that the absence of Rad can modulate the LTCC without contribution of β1,β2-AR signaling and that Rad deletion supersedes β-AR signaling to the LTCC to enhance in vivo heart function.

A model of the single atrial cell: relation between calcium current and calcium release

1990 ◽  
Vol 240 (1297) ◽  
pp. 83-96 ◽  
Keyword(s):  
Calcium Current ◽  
Calcium Release ◽  
Cytosolic Calcium ◽  
Exchange Current ◽  
Fura 2 ◽  
Calcium Dependent ◽  
Calcium Indicators ◽  
Calcium Exchange ◽  
Atrial Cell ◽  
Dependent Processes

The hypothesis that calcium release from the sarcoplasmic reticulum in cardiac muscle is induced by rises in free cytosolic calcium (Fabiato 1983, Am. J. Physiol 245) allows the possibility that the release could be at least partly regenerative. There would then be a non-linear relation between calcium current and calcium release. We have investigated this possibility in a single-cell version of the rabbit-atrial model developed by Hilgemann & Noble (1987, Proc. R. Soc. Lond . B 230). The model predicts different voltage ranges of activation for calcium-dependent processes (like the sodium-calcium exchange current, contraction or Fura-2 signals) and the calcium current, in agreement with the experimental results obtained by Earm et al . (1990, Proc. R. Soc. Lond . B 240) on exchange current tails, Cannell et al . (1987, Science, Wash . 238) by using Fura-2 signals, and Fedida et al . (1987, J. Physiol., Lond . 385) and Talo et al . (1988, Biology of isolated adult cardiac myocytes ) by using contraction. However, when the Fura-2 concentration is sufficiently high (greater than 200 μm) the activation ranges become very similar as the buffering properties of Fura-2 are sufficient to remove the regenerative effect. It is therefore important to allow for the buffering properties of calcium indicators when investigating the correlation between calcium current and calcium release.

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