Calcium channels: Structure, function, and classification

Perez‐Reyes, Edward; Schneider, Toni

doi:10.1002/ddr.430330311

Cited by 119 publications

(97 citation statements)

References 126 publications

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“…Functional expression in Xenopus oocytes has not only been used to define structure-function relations of voltage-gated calcium channels by assessing the effects of specific mutations of the ␣ 1 channel protein, but also to define identity and roles of the regulatory subunits in promoting ␣ 1 expression or modifying the properties of the expressed ␣ 1 subunit. Several nonallelic genes encoding ␣ 1 subunits, termed ␣ 1S and ␣ 1A -␣ 1E , have been identified by molecular cloning (1)(2)(3)(4). Of these, all except ␣ 1S have been functionally expressed in the Xenopus oocyte.…”

mentioning

confidence: 99%

A Xenopus oocyte β subunit: Evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit

Tareilus

Roux

Qin

et al. 1997

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

170

155

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Two closely related ␤ subunit mRNAs (xo28 and xo32) were identified in Xenopus oocytes by molecular cloning. One or both appear to be expressed as active proteins, because: (i) injection of Xenopus ␤ antisense oligonucleotides, but not of sense or unrelated oligonucleotides, significantly reduced endogenous oocyte voltage-gated Ca 2؉ channel (VGCC) currents and obliterated VGCC currents that arise after injection of mammalian ␣ 1 cRNAs (␣ 1C and ␣ 1E ); (ii) coinjection of a Xenopus ␤ antisense oligonucleotide and excess rat ␤ cRNA rescued expression of ␣ 1 Ca 2؉ channel currents; and (iii) coinjection of mammalian ␣ 1 cRNA with cRNA encoding either of the two Xenopus ␤ subunits facilitated both activation and inactivation of Ca 2؉ channel currents by voltage, as happens with most mammalian ␤ subunits. The Xenopus ␤ subunit cDNAs (␤3xo cDNAs) predict proteins of 484 aa that differ in only 22 aa and resemble most closely the sequence of the mammalian type 3 ␤ subunit. We propose that ''␣ 1 alone'' channels are in fact tightly associated ␣ 1 ␤3xo channels, and that effects of exogenous ␤ subunits are due to formation of higher-order [␣ 1 ␤]␤ n complexes with an unknown contribution of ␤3xo. It is thus possible that functional mammalian VGCCs, rather than having subunit composition ␣ 1 ␤, are [␣ 1 ␤]␤ n complexes that associate with ␣ 2 ␦ and, as appropriate, other tissue-specific accessory proteins. In support of this hypothesis, we discovered that the last 277-aa of ␣ 1E have a ␤ subunit binding domain. This ␤ binding domain is distinct from the previously known interaction domain located between repeats I and II of calcium channel ␣ 1 subunits.Xenopus oocytes translate exogenously injected mRNAs and cRNAs with relatively high efficiency. This has made them systems of choice for the functional expression and characterization of many cloned molecules, such as neuronal ligandgated ion channels, G protein-coupled receptors, and many voltage-gated ion channels, including voltage-dependent Ca 2ϩ channels. Voltage-dependent Ca 2ϩ channels are formed of an ␣ 1 pore-forming and voltage-sensing subunit and ␤ and ␣ 2 ␦ regulatory subunits. Functional expression in Xenopus oocytes has not only been used to define structure-function relations of voltage-gated calcium channels by assessing the effects of specific mutations of the ␣ 1 channel protein, but also to define identity and roles of the regulatory subunits in promoting ␣ 1 expression or modifying the properties of the expressed ␣ 1 subunit. Several nonallelic genes encoding ␣ 1 subunits, termed ␣ 1S and ␣ 1A -␣ 1E , have been identified by molecular cloning (1-4). Of these, all except ␣ 1S have been functionally expressed in the Xenopus oocyte. However, while certain variants of ␣ 1C and ␣ 1E can be expressed without coinjection of other subunit cRNAs (e.g., refs. 5 and 6), others, particularly ␣ 1A , yield only minimal currents in the absence of additional subunits, notably a ␤ subunit (7,8). The reasons for these differences are not understood.The interpreta...

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mentioning

confidence: 99%

A Xenopus oocyte β subunit: Evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit

Tareilus

Roux

Qin

et al. 1997

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

170

155

View full text Add to dashboard Cite

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“…The contribution of VGCD channel subtypes to information encoding varies adaptively, however. Intracellular signaling compounds, whose concentrations are elevated in response to activity, functionally modulate the kinetics and maximum conductances of VGCD channels (Perezreyes and Schneider 1994, Kallen et al 1993, Li et al 1993, Toro and Stefani 1991, Numann et al 1991, Chetkovich et al 1991. A significant body of work in Aplysia suggests that some forms of animal learning can be attributed to the activity-dependent modulations of VGCD channels (Klein and Kandel 1978, Fitzgerald et al 1990, Edmonds et al 1990.…”

Section: The Problem In Neurosciencementioning

confidence: 99%

“…The matrix is sparse and constant (with respect to the location of zeros) for a given discretized morphology (Hines 1984, Mascagni 1989, Eichler West and Wilcox 1996. Numerical methods optimized for sparse matrices, such as the minimal ordering method, eliminate unnecessary operations on zerovalued matrix elements (Press et al 1992).…”

Section: High Performance Computing Aspects Of the Problemmentioning

confidence: 99%

Using Evolutionary Algorithms to Search for Control Parameters in a Nonlinear Partial Differential Equation

West

Schutter

Wilcox

1999

Evolutionary Algorithms

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Many physical systems of interest to scientists and engineers can be modeled using a partial differential equation extended along the dimensions of time and space. These equations are typically nonlinear with real-valued parameters that control the classes of behaviors that the model is able to produce. Unfortunately, these control parameters are often difficult to measure in the physical system. Consequently, the first task in developing a model is usually to search for appropriate parameter values. In a high dimensional system, this task potentially requires a prohibitive number of evaluations and it may be impossible or inappropriate to select a unique solution. We have applied evolutionary algorithms (EAs) to the problem of parameter selection in models of biologically realistic neurons. Our objective was not to find the "best" solution, but rather we sought to produce the manifold of high fitness solutions that best accounts for biological variability. The search space was high dimensional (> 100) and each function evaluation required from one minute to several hours of CPU time on high performance computers. Using this model and our goals as an example, we will: 1) review the problem from the neuroscience perspective; 2) discuss high performance computing aspects of the problem; 3) examine the suitability of EAs for the efficient optimization of this class of problems; and 4) describe and justify the specific EA implementation used to solve this problem.

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“…Neuronal Ca 2+ channels are composed of a central poreforming c~l subunit associated with at least 2 different auxiliary subunits ¢x2-8 and I~ [10][11][12]. The ctl subunit specifies the gating kinetics and the pharmacological profile of the channel [4,13].…”

Section: Introductionmentioning

confidence: 99%

“…Each of the [3 subunits (four genes identified to date) modulates specifically the kinetics and the voltage-dependent gating of the al subunit [3,[14][15][16]. The ct2-8 subunit (only one gene identified so far, [11]) seems to have only minor regulatory role on cd current properties.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the α1A Ca²⁺ channel by β subunits at physiological Ca²⁺ concentration

et al. 1996

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The class A Ca 2+ channel ¢xl snbunit (cdA) was expressed in Xenopus oocytes alone or in combination with the I~lb, l~2a, 113, or I]4 subunit. Analysis of voltage-dependent activation and inactivation in the presence of 1.8 mM external Ca 2+ showed an hyperpolarising shift of both relations when compared to similar recordings performed in the presence of 40 mM Ba 2+. These shifts, which differed for activation and inactivation, were strongly modulated by the nature of the coexpressed ~ subunit. On the other hand, for each combination, the kinetics of inactivation were similar in 1.8 mM Ca 2+ and 40 mM Ba z+ (for example co-expression of the l~2a subuult reduced inactivation using either 40 mM Ba 2+ or 1.8 mM Ca2+). Thus, modulation of channel properties by the ~ subunit is different in physiological Ca 2+ or high Ba 2÷ concentrations. These results must be taken into consideration to extrapolate the role of the subunit in native cells.

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Calcium channels: Structure, function, and classification

Cited by 119 publications

References 126 publications

A Xenopus oocyte β subunit: Evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit

A Xenopus oocyte β subunit: Evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit

Using Evolutionary Algorithms to Search for Control Parameters in a Nonlinear Partial Differential Equation

Modulation of the α1A Ca²⁺ channel by β subunits at physiological Ca²⁺ concentration

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Calcium channels: Structure, function, and classification

Cited by 119 publications

References 126 publications

A Xenopus oocyte β subunit: Evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit

A Xenopus oocyte β subunit: Evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit

Using Evolutionary Algorithms to Search for Control Parameters in a Nonlinear Partial Differential Equation

Modulation of the α1A Ca2+ channel by β subunits at physiological Ca2+ concentration

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Modulation of the α1A Ca²⁺ channel by β subunits at physiological Ca²⁺ concentration