Voltage- and calcium-dependent inactivation in high voltage-gated Ca2+ channels

Cens, Thierry; Rousset, Matthieu; Leyris, Jean-Philippe; Fesquet, P.; Charnet, Pierre

doi:10.1016/j.pbiomolbio.2005.05.013

Cited by 105 publications

(120 citation statements)

References 63 publications

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“…Ca 2+ channel β-subunits have a major influence on the cell surface expression, kinetics, and voltage dependence of gating of Ca 2+ channels (28). To determine how Ca 2+ channel β-subunit composition alters I Async , we compared I Async conducted by slowly inactivating Ca V 2.1 channels containing the β 2a -subunit with rapidly inactivating channels containing the β 1b -subunit expressed in tsA-201 cells.…”

Section: Resultsmentioning

confidence: 99%

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Few¹,

Nanou²,

Watari

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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We have identified an asynchronously activated Ca 2+ current through voltage-gated Ca 2+ (Ca V )-2.1 and Ca V 2.2 channels, which conduct P/Qand N-type Ca 2+ currents that initiate neurotransmitter release. In nonneuronal cells expressing Ca V 2.1 or Ca V 2.2 channels and in hippocampal neurons, prolonged Ca 2+ entry activates a Ca 2+ current, I Async , which is observed on repolarization and decays slowly with a halftime of 150-300 ms. I Async is not observed after L-type Ca 2+ currents of similar size conducted by Ca V 1.2 channels. I Async is Ca 2+ -selective, and it is unaffected by changes in Na + , K + , Cl − , or H + or by inhibitors of a broad range of ion channels. During trains of repetitive depolarizations, I Async increases in a pulse-wise manner, providing Ca 2+ entry that persists between depolarizations. In single-cultured hippocampal neurons, trains of depolarizations evoke excitatory postsynaptic currents that show facilitation followed by depression accompanied by asynchronous postsynaptic currents that increase steadily during the train in parallel with I Async . I Async is much larger for slowly inactivating Ca V 2.1 channels containing β 2a -subunits than for rapidly inactivating channels containing β 1b -subunits. I Async requires global rises in intracellular Ca 2+ , because it is blocked when Ca 2+ is chelated by 10 mM EGTA in the patch pipette. Neither mutations that prevent Ca 2+ binding to calmodulin nor mutations that prevent calmodulin regulation of Ca V 2.1 block I Async . The rise of I Async during trains of stimuli, its decay after repolarization, its dependence on global increases of Ca 2+ , and its enhancement by β 2a -subunits all resemble asynchronous release, suggesting that I Async is a Ca 2+ source for asynchronous neurotransmission.asynchronous synaptic transmission | exocytosis V oltage-gated Ca 2+ (Ca V ) channels are activated by depolarization and conduct inward Ca 2+ currents that initiate many cellular responses to electrical signaling (1). Ca V 2 channels conduct P/Q-, N-, and R-type currents in presynaptic nerve terminals, and Ca 2+ entry through these channels initiates neurotransmitter release at conventional synapses (1-3). P/Q-and N-type Ca 2+ currents conducted by Ca V 2.1 and Ca V 2.2 channels, respectively, are more efficiently coupled to neurotransmitter release than Rtype Ca 2+ currents conducted by Ca V 2.3 channels (4, 5). Neurotransmitter release occurs in two phases: a fast synchronous (phasic) component and a slow asynchronous (tonic) component (6). The slower asynchronous component of release is proposed to result from residual Ca 2+ remaining after an action potential acting on a different Ca 2+ sensor than the sensor for synchronous neurotransmitter release (6-8). Remarkably, when synchronous release is prevented by deletion of its Ca 2+ sensor synaptotagmin, the asynchronous release process can cause exocytosis of the entire readily releasable pool, suggesting a functional competition between synchronous and asynchronous release processes for the ...

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Section: Resultsmentioning

confidence: 99%

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Few¹,

Nanou²,

Watari

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Elimination of CDI in Ca V 1.3 IQ⌬ channels is independent of ␤-subunit isoform It is well known that different auxiliary ␤ subunit isoforms can produce different voltage-dependent inactivation (Cens et al, 2006). To determine whether the amount of CDI experienced by Ca V 1.3 IQ⌬ and Ca V 1.3 IQfull channels might be influenced by the type of ␤-subunit present, we explicitly characterized both channel types during coexpression with various rat ␤-subunits (other than the rat ␤ 2a already used in Fig.…”

Section: Resultsmentioning

confidence: 99%

Alternative Splicing of the Ca_V1.3 Channel IQ Domain, a Molecular Switch for Ca²⁺-Dependent Inactivation within Auditory Hair Cells

Shen¹,

Yu²,

Hiel³

et al. 2006

J. Neurosci.

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Native Ca V 1.3 channels within cochlear hair cells exhibit a surprising lack of Ca 2ϩ -dependent inactivation (CDI), given that heterologously expressed Ca V 1.3 channels show marked CDI. To determine whether alternative splicing at the C terminus of the Ca V 1.3 gene may produce a hair cell splice variant with weak CDI, we transcript-scanned mRNA obtained from rat cochlea. We found that the alternate use of exon 41 acceptor sites generated a splice variant that lost the calmodulin-binding IQ motif of the C terminus. These Ca V 1.3 IQ⌬ ("IQ deleted") channels exhibited a lack of CDI, which was independent of the type of coexpressed ␤-subunits. Ca V 1.3 IQ⌬ channel immunoreactivity was preferentially localized to cochlear outer hair cells (OHCs), whereas that of Ca V 1.3 IQfull channels (IQ-possessing) labeled inner hair cells (IHCs). The preferential expression of Ca V 1.3 IQ⌬ within OHCs suggests that these channels may play a role in processes such as electromotility or activity-dependent gene transcription rather than neurotransmitter release, which is performed predominantly by IHCs in the cochlea.

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“…Inactivation of Ca 2+ channels is complex and mediated by several voltage-dependent and Ca 2+ -dependent mechanisms. [78][79][80] The precise molecular correlates of inactivation remain somewhat unclear, but fast voltage-dependent inactivation might involve a "hinged lid" type mechanism, with the intracellular loop connecting domains I and II of the α 1 -subunit serving the role of the "inactivation gate" (reviewed in ref. 79, 81 and 82).…”

Section: Subunits-functional Effectsmentioning

confidence: 99%

G protein inhibition of Ca_V2 calcium channels

Currie¹

2010

Channels

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Voltage- and calcium-dependent inactivation in high voltage-gated Ca2+ channels

Cited by 105 publications

References 63 publications

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Alternative Splicing of the Ca_V1.3 Channel IQ Domain, a Molecular Switch for Ca²⁺-Dependent Inactivation within Auditory Hair Cells

G protein inhibition of Ca_V2 calcium channels

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Voltage- and calcium-dependent inactivation in high voltage-gated Ca2+ channels

Cited by 105 publications

References 63 publications

Asynchronous Ca 2 + current conducted by voltage-gated Ca 2+ (Ca V )-2.1 and Ca V 2.2 channels and its implications for asynchronous neurotransmitter release

Asynchronous Ca 2 + current conducted by voltage-gated Ca 2+ (Ca V )-2.1 and Ca V 2.2 channels and its implications for asynchronous neurotransmitter release

Alternative Splicing of the CaV1.3 Channel IQ Domain, a Molecular Switch for Ca2+-Dependent Inactivation within Auditory Hair Cells

G protein inhibition of CaV2 calcium channels

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Product

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Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Alternative Splicing of the Ca_V1.3 Channel IQ Domain, a Molecular Switch for Ca²⁺-Dependent Inactivation within Auditory Hair Cells

G protein inhibition of Ca_V2 calcium channels