Expression and Modulation of an Invertebrate Presynaptic Calcium Channel α1 Subunit Homolog

Spafford, J. David; Chen, Lina; Feng, Zhong‐Ping; Smit, August B.; Zamponi, Gerald W.

doi:10.1074/jbc.m302212200

Cited by 41 publications

(61 citation statements)

References 66 publications

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“…Transfected LCa v 2a cDNA contained the first 44 amino acids swapped with the homologous region of rat Ca v 2.1. We demonstrated previously (27) that this alteration is one that is both necessary and sufficient for membrane expression of LCa v 2a in human cell lines. The activities of calcium channels were measured with barium as the charge carrier via whole cell patch clamp using an Axopatch 200B amplifier (Axon Instruments, Union City, CA), pCLAMP 9.0 software, after incubation of transiently transfected cells at 28°C for 2-4 days.…”

Section: Molecular Identification Structural Analyses and Preparatimentioning

confidence: 99%

“…The activities of calcium channels were measured with barium as the charge carrier via whole cell patch clamp using an Axopatch 200B amplifier (Axon Instruments, Union City, CA), pCLAMP 9.0 software, after incubation of transiently transfected cells at 28°C for 2-4 days. All solutions and recording procedures have been described previously (27).…”

Section: Molecular Identification Structural Analyses and Preparatimentioning

confidence: 99%

“…Transfection and Assessment of Function in Vitro by Patch Clamp Electrophysiology-Heterologously expressed cDNAs encoding an enhanced green fluorescent protein marker (Clontech), a Ca v 2 ␣ 1 subunit from rat (rCa v 2.1, rCa v 2.2, and rCa v 2.3) or Lymnaea (LCa v 2a, GenBank TM accession number AF484082), the rat ␣ 2 -␦ 1 subunit, and either no ␤ subunit or one of the four rat ␤ subunits (␤ 1b , ␤ 2a , ␤ 3 , and ␤ 4 ) or the Lymnaea ␤ subunit (LCav␤) were transfected into human embryonic kidney tsA-201 cells by using a standard calcium phosphate protocol (27). Transfected LCa v 2a cDNA contained the first 44 amino acids swapped with the homologous region of rat Ca v 2.1.…”

Section: Molecular Identification Structural Analyses and Preparatimentioning

confidence: 99%

“…We have reported recently the isolation and functional characterization of a Ca v 2 calcium channel homolog (LCa v 2) from the mollusc Lymnaea stagnalis. We showed that LCa v 2 displays functional properties that are reminiscent of mammalian Ntype calcium channels (27) and that this channel is essential for synaptic transmission between identified Lymnaea neurons (4). Like its vertebrate counterpart, LCa v 2 contains the ␣-interaction domain, a highly conserved region in the domain I-II linker that is essential for interactions with calcium channel ␤ subunits (4,27).…”

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confidence: 99%

“…We showed that LCa v 2 displays functional properties that are reminiscent of mammalian Ntype calcium channels (27) and that this channel is essential for synaptic transmission between identified Lymnaea neurons (4). Like its vertebrate counterpart, LCa v 2 contains the ␣-interaction domain, a highly conserved region in the domain I-II linker that is essential for interactions with calcium channel ␤ subunits (4,27). Furthermore, the Lymnaea model system allows for the in vitro reconstruction of identified synapses, which are highly amenable for molecular and cellular manipulation.…”

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confidence: 99%

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Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons

Spafford

Minnen

Larsen

et al. 2004

Journal of Biological Chemistry

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Calcium channel ␤ subunits are key modulators of calcium channel function and membrane targeting of the pore-forming ␣ 1 subunit. Here we show that an invertebrate (Lymnaea stagnalis) homolog of P/Q-and Ntype calcium channels (LCa v 2), although colocalized with ␤ subunits in synapses of mature neurons, is physically uncoupled from the ␤ subunits in the leading edge of growth cones of outgrowing neurons. Moreover, LCa v 2 channels that mediate transmitter release in mature synapses also participate in neuronal outgrowth in growth cones. The differential association of ␤ subunits with synaptic calcium channels and those expressed in emergent neuronal growth suggests that ␤ subunits may play a role in the transformation of Ca v 2 calcium channel function in immature neurons and mature synapses.

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Section: Molecular Identification Structural Analyses and Preparatimentioning

confidence: 99%

Section: Molecular Identification Structural Analyses and Preparatimentioning

confidence: 99%

Section: Molecular Identification Structural Analyses and Preparatimentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons

Spafford

Minnen

Larsen

et al. 2004

Journal of Biological Chemistry

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Interactions with PDZ proteins diversify voltage‐gated calcium channel signaling

Wang

Cortés

2020

J of Neuroscience Research

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Voltage‐gated Ca2+ (CaV) channels are crucial for neuronal excitability and synaptic transmission upon depolarization. Their properties in vivo are modulated by their interaction with a variety of scaffolding proteins. Such interactions can influence the function and localization of CaV channels, as well as their coupling to intracellular second messengers and regulatory pathways, thus amplifying their signaling potential. Among these scaffolding proteins, a subset of PDZ (postsynaptic density‐95, Drosophila discs‐large, and zona occludens)‐domain containing proteins play diverse roles in modulating CaV channel properties. At the presynaptic terminal, PDZ proteins enrich CaV channels in the active zone, enabling neurotransmitter release by maintaining a tight and vital link between channels and vesicles. In the postsynaptic density, these interactions are essential in regulating dendritic spine morphology and postsynaptic signaling cascades. In this review, we highlight the studies that demonstrate dynamic regulations of neuronal CaV channels by PDZ proteins. We discuss the role of PDZ proteins in controlling channel activity, regulating channel cell surface density, and influencing channel‐mediated downstream signaling events. We highlight the importance of PDZ protein regulations of CaV channels and evaluate the link between this regulatory effect and human disease.

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Ca_v3 T‐type calcium channels

Senatore

Zhorov

Spafford

2012

WIREs Membr Transp Signal

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T-type channels are unique among the voltage-gated calcium channels in their fast kinetics and low voltages of activation and inactivation, the latter two features allowing them to operate at voltages near the resting membrane potential of most neurons. T-type channels can therefore be recruited by subthreshold depolarizations, and hyperpolarizations that remove inactivation. As such, T-type channels can significantly influence how and when cells reach action potential threshold, and thus are critical regulators of excitability. T-type channels are also significantly conserved within the animal kingdom, present even in animals lacking muscles and nerves, suggesting that they evolved before or very early on during the emergence of neuronal and neuromuscular synapses. Physiologically, T-type channels are involved in multiple processes, and their contributions range from purely electrogenic roles to the activation of calcium-sensitive ion channels, signaling pathways, and other macromolecular complexes. Unfortunately, it has been difficult to prove sufficiency and necessity of T-type channels in many of these processes, in part due to inconsistencies in their suspected contributions. INTRODUCTION Voltage-gated calcium channels of the Ca v 3 family, or T-type calcium channels, likely evolved in animals either before or during the very early stages of nervous system evolution, and were subsequently adapted for electrical excitability and calcium signaling in different cell types including neurons, muscle and secretory cells. Although intensively studied, the lack of specific blockers has made it difficult to ascribe T-type channels with specific functions. Recent advances in imaging and electrophysiological techniques, along with the discovery of novel-blocking compounds and the * Correspondence to: spafford@uwaterloo.ca 1 Department of Biology, University of Waterloo, Waterloo, Ontario, Canada 2 Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada development of molecular and biological tools, have paved the way for accelerated discovery. A clearer picture is emerging, where T-type channel functions are ascribed to particular Ca v 3 isotype(s), and which vary depending on the configuration of calcium-sensitive factors (i.e., calcium-sensitive signaling pathways and ionic conductances) present in cells, and also on the electrical properties of cells as determined by other ion channels, receptors, and pumps. HISTORY OF T-TYPE CURRENT ISOLATIONT-type calcium currents were first isolated in the 1970s by Susumu Hagiwara in invertebrate starfish eggs using two-electrode voltage clamp.1 'Channel I' currents were evoked by small depolarizations, (Figure 1(a)). Subsequent voltage clamp studies also identified channel I currents in vertebrate preparations, including guinea-pig inferior olivary 2 and thalamic neurons 3 and chick sensory neurons. 4 The term 'T-type channel' was coined on the basis of the transient (rapid) kinetics and tiny unitary conductance of channel I type cur...

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Expression and Modulation of an Invertebrate Presynaptic Calcium Channel α1 Subunit Homolog

Cited by 41 publications

References 66 publications

Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons

Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons

Interactions with PDZ proteins diversify voltage‐gated calcium channel signaling

Ca_v3 T‐type calcium channels

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Expression and Modulation of an Invertebrate Presynaptic Calcium Channel α1 Subunit Homolog

Cited by 41 publications

References 66 publications

Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons

Uncoupling of Calcium Channel α1 and β Subunits in Developing Neurons

Interactions with PDZ proteins diversify voltage‐gated calcium channel signaling

Cav3 T‐type calcium channels

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Product

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Ca_v3 T‐type calcium channels