scholarly journals Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus

eNeuro ◽  
2018 ◽  
Vol 5 (1) ◽  
pp. ENEURO.0016-18.2018 ◽  
Author(s):  
Tamara Timic Stamenic ◽  
Slobodan M. Todorovic
Keyword(s):  
Calcium Channels ◽  
Medial Thalamus ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Excitability Of Neurons

Halothane Inhibition of Recombinant Cardiac L-type Ca2+ Channels Expressed in HEK-293 Cells

2005 ◽  
Vol 103 (6) ◽  
pp. 1156-1166 ◽  
Author(s):  
Kevin J. Gingrich ◽  
Son Tran ◽  
Igor M. Nikonorov ◽  
Thomas J. Blanck
Keyword(s):  
Charge Transfer ◽  
Calcium Channels ◽  
Dependent Manner ◽  
Current Time ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Dependent Inactivation ◽  
Voltage Dependent

Background Volatile anesthetics depress cardiac contractility, which involves inhibition of cardiac L-type calcium channels. To explore the role of voltage-dependent inactivation, the authors analyzed halothane effects on recombinant cardiac L-type calcium channels (alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1), which differ by the alpha2/delta1 subunit and consequently voltage-dependent inactivation. Methods HEK-293 cells were transiently cotransfected with complementary DNAs encoding alpha1C tagged with green fluorescent protein and beta2a, with and without alpha2/delta1. Halothane effects on macroscopic barium currents were recorded using patch clamp methodology from cells expressing alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1 as identified by fluorescence microscopy. Results Halothane inhibited peak current (I(peak)) and enhanced apparent inactivation (reported by end pulse current amplitude of 300-ms depolarizations [I300]) in a concentration-dependent manner in both channel types. alpha2/delta1 coexpression shifted relations leftward as reported by the 50% inhibitory concentration of I(peak) and I300/I(peak)for alpha1Cbeta2a (1.8 and 14.5 mm, respectively) and alpha1Cbeta2aalpha2/delta1 (0.74 and 1.36 mm, respectively). Halothane reduced transmembrane charge transfer primarily through I(peak) depression and not by enhancement of macroscopic inactivation for both channels. Conclusions The results indicate that phenotypic features arising from alpha2/delta1 coexpression play a key role in halothane inhibition of cardiac L-type calcium channels. These features included marked effects on I(peak) inhibition, which is the principal determinant of charge transfer reductions. I(peak) depression arises primarily from transitions to nonactivatable states at resting membrane potentials. The findings point to the importance of halothane interactions with states present at resting membrane potential and discount the role of inactivation apparent in current time courses in determining transmembrane charge transfer.

scholarly journals CaBP1 Regulates Voltage-dependent Inactivation and Activation of CaV1.2 (L-type) Calcium Channels

2011 ◽  
Vol 286 (16) ◽  
pp. 13945-13953 ◽  
Author(s):  
Shimrit Oz ◽  
Vladimir Tsemakhovich ◽  
Carl J. Christel ◽  
Amy Lee ◽  
Nathan Dascal
Keyword(s):  
Calcium Channels ◽  
Dependent Inactivation ◽  
Voltage Dependent

Molecular determinants of voltage-dependent inactivation in calcium channels

Nature ◽  
1994 ◽  
Vol 372 (6501) ◽  
pp. 97-100 ◽  
Author(s):  
Ji-Fang Zhang ◽  
Patrick T. Ellinor ◽  
Richard W. Aldrich ◽  
Richard W. Tsien
Keyword(s):  
Calcium Channels ◽  
Dependent Inactivation ◽  
Molecular Determinants ◽  
Voltage Dependent

scholarly journals Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels

2010 ◽  
Vol 299 (5) ◽  
pp. C1203-C1211 ◽  
Author(s):  
Kai Guo ◽  
Xianming Wang ◽  
Guofeng Gao ◽  
Congxin Huang ◽  
Keith S. Elmslie ◽  
...  
Keyword(s):  
Amino Acid ◽  
Calcium Channels ◽  
Molecular Mechanisms ◽  
Channel Gating ◽  
Fine Tuning ◽  
Amino Acid Substitutions ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Kinetics Of

We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149–1159, 2010). The short 17 amino acid extracellular NH2-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate CaV1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with CaV1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on CaV1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca2+ dynamics in the heart.

Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels

2000 ◽  
Vol 39 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Cristina Jiménez ◽  
Emmanuel Bourinet ◽  
Valérie Leuranguer ◽  
Sylvain Richard ◽  
Terry P Snutch ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Dependent Inactivation ◽  
Voltage Dependent

scholarly journals Involvement of the Carboxyl-terminal Region of the Subunit in Voltage-dependent Inactivation of Cardiac Calcium Channels

1995 ◽  
Vol 270 (29) ◽  
pp. 17306-17310 ◽  
Author(s):  
Udo Klöckner ◽  
Gabor Mikala ◽  
Maria Varadi ◽  
Gyula Varadi ◽  
Arnold Schwartz
Keyword(s):  
Calcium Channels ◽  
Terminal Region ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Carboxyl Terminal

scholarly journals Voltage-dependent inactivation of T-tubular skeletal calcium channels in planar lipid bilayers.

1991 ◽  
Vol 97 (2) ◽  
pp. 393-412 ◽  
Author(s):  
R Mejía-Alvarez ◽  
M Fill ◽  
E Stefani
Keyword(s):  
Calcium Channels ◽  
Lipid Bilayers ◽  
Single Channel ◽  
Channel Activity ◽  
T Tube ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Single Channel Activity ◽  
Kinetics Of ◽  
Channel Properties

Single-channel properties of dihydropyridine (DHP)-sensitive calcium channels isolated from transverse tubular (T-tube) membrane of skeletal muscle were explored. Single-channel activity was recorded in planar lipid bilayers after fusion of highly purified rabbit T-tube microsomes. Two populations of DHP-sensitive calcium channels were identified. One type of channel (noninactivating) was active (2 microM +/- Bay K 8644) at steady-state membrane potentials and has been studied in other laboratories. The second type of channel (inactivating) was transiently activated during voltage pulses and had a very low open probability (Po) at steady-state membrane potentials. Inactivating channel activity was observed in 47.3% of the experiments (n = 84 bilayers). The nonstationary kinetics of this channel was determined using a standard voltage pulse (HP = -50 mV, pulse to 0 mV). The time constant (tau) of channel activation was 23 ms. During the mV). The time constant (tau) of channel activation was 23 ms. During the pulse, channel activity decayed (inactivated) with a tau of 3.7 s. Noninactivating single-channel activity was well described by a model with two open and two closed states. Inactivating channel activity was described by the same model with the addition of an inactivated state as proposed for cardiac muscle. The single-channel properties were compared with the kinetics of DHP-sensitive inward calcium currents (ICa) measured at the cellular level. Our results support the hypothesis that voltage-dependent inactivation of single DHP-sensitive channels contributes to the decay of ICa.

Inactivation Properties of Human Recombinant Class E Calcium Channels

2000 ◽  
Vol 83 (2) ◽  
pp. 671-684 ◽  
Author(s):  
Anne Jouvenceau ◽  
Federica Giovannini ◽  
Cath P. Bath ◽  
Emily Trotman ◽  
Emanuele Sher
Keyword(s):  
Calcium Channels ◽  
Low Voltage ◽  
Channel Blockers ◽  
Pharmacological Properties ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Hek 293 ◽  
Clear Cut ◽  
Dependent Inactivation ◽  
Voltage Dependent

The electrophysiological and pharmacological properties of α1E-containing Ca2+ channels were investigated by using the patch-clamp technique in the whole cell configuration, in HEK 293 cells stably expressing the human α1E together with α2b and β1baccessory subunits. These channels had current-voltage ( I-V) characteristics resembling those of high-voltage–activated (HVA) Ca2+ channels (threshold at −30 mV and peak amplitude at +10 mV in 5 mM Ca2+). The currents activated and deactivated with a fast rate, in a time- and voltage-dependent manner. No difference was found in their relative permeability to Ca2+ and Ba2+. Inorganic Ca2+ channel blockers (Cd2+, Ni2+) blocked completely and potently the α1E,/α2bδ/β1b mediated currents (IC50 = 4 and 24.6 μM, respectively). α1E-mediated currents inactivated rapidly and mainly in a non–Ca2+-dependent manner, as evidenced by the fact that 1) decreasing extracellular Ca2+ from 10 to 2 mM and 2) changing the intracellular concentration of the Ca2+ chelator 1.2-bis(2-aminophenoxy) ethane- N,N,N′,N′-tetraacetic acid (BAPTA), did not affect the inactivation characteristics; 3) there was no clear-cut bell-shaped relationship between test potential and inactivation, as would be expected from a Ca2+-dependent event. Although Ba2+ substitution did not affect the inactivation of α1E channels, Na+substitution revealed a small but significant reduction in the extent and rate of inactivation, suggesting that besides the presence of dominant voltage-dependent inactivation, α1E channels are also affected by a divalent cation-dependent inactivation process. We have analyzed the Ca2+ currents produced by a range of imposed action potential–like voltage protocols (APVPs). The amplitude and area of the current were dependent on the duration of the waveform employed and were relatively similar to those described for HVA calcium channels. However, the peak latency resembled that obtained for low-voltage–activated (LVA) calcium channels. Short bursts of APVPs applied at 100 Hz produced a depression of the Ca2+ current amplitude, suggesting an accumulation of inactivation likely to be calcium dependent. The human α1E gene seems to participate to a Ca2+ channel type with biophysical and pharmacological properties partly resembling those of LVA and those of HVA channels, with inactivation characteristics more complex than previously believed.

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