scholarly journals The L-type calcium channel C-terminus: sparking interest beyond its role in calcium-dependent inactivation

2003 ◽  
Vol 552 (2) ◽  
pp. 333-333 ◽  
Author(s):  
G. W. Zamponi
Keyword(s):  
Calcium Channel ◽  
Calcium Dependent ◽  
C Terminus ◽  
Dependent Inactivation

scholarly journals Single-Channel Mechanism of Modulation of Calcium-Dependent Inactivation of the Voltage-Gated Calcium Channel Cav1.3 by its C-Terminus

2013 ◽  
Vol 104 (2) ◽  
pp. 459a
Author(s):  
Elena Novikova ◽  
Elza Kuzmenkina ◽  
Wanchana Jangsangthong ◽  
Jan Matthes ◽  
Alexandra Koschak ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Single Channel ◽  
Voltage Gated ◽  
Calcium Dependent ◽  
C Terminus ◽  
Dependent Inactivation ◽  
Voltage Gated Calcium Channel

scholarly journals STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-dependent inactivation

2018 ◽  
Vol 115 (6) ◽  
pp. 1376-1381 ◽  
Author(s):  
Marta Campiglio ◽  
Pierre Costé de Bagneaux ◽  
Nadine J. Ortner ◽  
Petronel Tuluc ◽  
Filip Van Petegem ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Calcium Channel ◽  
Muscle Disease ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Calcium Dependent ◽  
C Terminus ◽  
Dependent Inactivation ◽  
C1 Domain

The adaptor proteins STAC1, STAC2, and STAC3 represent a newly identified family of regulators of voltage-gated calcium channel (CaV) trafficking and function. The skeletal muscle isoform STAC3 is essential for excitation–contraction coupling and its mutation causes severe muscle disease. Recently, two distinct molecular domains in STAC3 were identified, necessary for its functional interaction with CaV1.1: the C1 domain, which recruits STAC proteins to the calcium channel complex in skeletal muscle triads, and the SH3-1 domain, involved in excitation–contraction coupling. These interaction sites are conserved in the three STAC proteins. However, the molecular domain in CaV1 channels interacting with the STAC C1 domain and the possible role of this interaction in neuronal CaV1 channels remained unknown. Using CaV1.2/2.1 chimeras expressed in dysgenic (CaV1.1−/−) myotubes, we identified the amino acids 1,641–1,668 in the C terminus of CaV1.2 as necessary for association of STAC proteins. This sequence contains the IQ domain and alanine mutagenesis revealed that the amino acids important for STAC association overlap with those making contacts with the C-lobe of calcium-calmodulin (Ca/CaM) and mediating calcium-dependent inactivation of CaV1.2. Indeed, patch-clamp analysis demonstrated that coexpression of either one of the three STAC proteins with CaV1.2 opposed calcium-dependent inactivation, although to different degrees, and that substitution of the CaV1.2 IQ domain with that of CaV2.1, which does not interact with STAC, abolished this effect. These results suggest that STAC proteins associate with the CaV1.2 C terminus at the IQ domain and thus inhibit calcium-dependent feedback regulation of CaV1.2 currents.

scholarly journals A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eder Gambeta ◽  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
Gerald W. Zamponi
Keyword(s):  
Trigeminal Neuralgia ◽  
Missense Mutation ◽  
Neurotransmitter Release ◽  
Trigeminal System ◽  
Wild Type ◽  
Calcium Dependent ◽  
Whole Cell Patch Clamp ◽  
C Terminus ◽  
Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

scholarly journals A Selectivity Filter Gate Controls Voltage-Gated Calcium Channel Calcium-Dependent Inactivation

Neuron ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 1134-1149.e3 ◽  
Author(s):  
Fayal Abderemane-Ali ◽  
Felix Findeisen ◽  
Nathan D. Rossen ◽  
Daniel L. Minor
Keyword(s):  
Calcium Channel ◽  
Selectivity Filter ◽  
Voltage Gated ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Voltage Gated Calcium Channel

scholarly journals Disruption of the IS6-AID Linker Affects Voltage-gated Calcium Channel Inactivation and Facilitation

2009 ◽  
Vol 133 (3) ◽  
pp. 327-343 ◽  
Author(s):  
Felix Findeisen ◽  
Daniel L. Minor
Keyword(s):  
Calcium Channel ◽  
Common Mechanism ◽  
Interaction Domain ◽  
Voltage Gated ◽  
Calcium Dependent ◽  
Calcium Channel Inactivation ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Rigid Connection ◽  
Voltage Gated Calcium Channel

Two processes dominate voltage-gated calcium channel (CaV) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The CaVβ/CaVα1-I-II loop and Ca2+/calmodulin (CaM)/CaVα1–C-terminal tail complexes have been shown to modulate each, respectively. Nevertheless, how each complex couples to the pore and whether each affects inactivation independently have remained unresolved. Here, we demonstrate that the IS6–α-interaction domain (AID) linker provides a rigid connection between the pore and CaVβ/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate CaV1.2 (L-type) and CaV2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt CaVβ/I-II association sharply decelerate CDI and reduce a second Ca2+/CaM/CaVα1–C-terminal–mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, CaVβ and the IS6-AID linker, are essential for calcium-dependent modulation, and that both CaVβ-dependent and CaM-dependent components couple to the pore by a common mechanism requiring CaVβ and an intact IS6-AID linker.

scholarly journals Functional properties of cardiac L-type calcium channels transiently expressed in HEK293 cells. Roles of alpha 1 and beta subunits.

1995 ◽  
Vol 105 (2) ◽  
pp. 289-305 ◽  
Author(s):  
M T Pérez-García ◽  
T J Kamp ◽  
E Marbán
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channel ◽  
Binding Sites ◽  
Beta Subunit ◽  
Hek293 Cells ◽  
Beta Subunits ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Kinetics Of ◽  
Macroscopic Kinetics

The cardiac dihydropyridine-sensitive calcium channel was transiently expressed in HEK293 cells by transfecting the rabbit cardiac calcium channel alpha 1 subunit (alpha 1C) alone or in combination with the rabbit calcium channel beta subunit cloned from skeletal muscle. Transfection with alpha 1C alone leads to the expression of inward, voltage-activated, calcium or barium currents that exhibit dihydropyridine sensitivity and voltage- as well as calcium-dependent inactivation. Coexpression of the skeletal muscle beta subunit increases current density and the number of high-affinity dihydropyridine binding sites and also affects the macroscopic kinetics of the current. Recombinant alpha 1C beta channels exhibit a slowing of activation and a faster inactivation rate when either calcium or barium carries the charge. Our data suggest that both an increase in the number of channels as well as modulatory effects on gating underlie the modifications observed upon beta subunit coexpression.

scholarly journals Calcium-dependent inactivation of neuronal calcium channel currents is independent of calcineurin

Neuroscience ◽  
1999 ◽  
Vol 95 (1) ◽  
pp. 235-241 ◽  
Author(s):  
H.U. Zeilhofer ◽  
N.M. Blank ◽  
W.L. Neuhuber ◽  
D. Swandulla
Keyword(s):  
Calcium Channel ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Channel Currents ◽  
Neuronal Calcium Channel
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