scholarly journals Trpc1 as the Missing Link Between the Bmp and Ca2+ Signalling Pathways During Neural Specification in Amphibians

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Isabelle Néant ◽  
Ho Chi Leung ◽  
Sarah E. Webb ◽  
Andrew L. Miller ◽  
Marc Moreau ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Neural Induction ◽  
Receptor Potential ◽  
Physical Interaction ◽  
Morphogenetic Protein ◽  
Voltage Dependent ◽  
Neural Specification ◽  
Trpc1 Channels ◽  
Bmp Signalling ◽  
Transient Receptor

Abstract In amphibians, the inhibition of bone morphogenetic protein (BMP) in the dorsal ectoderm has been proposed to be responsible for the first step of neural specification, called neural induction. We previously demonstrated that in Xenopus laevis embryos, the BMP signalling antagonist, noggin, triggers an influx of Ca2+ through voltage-dependent L-type Ca2+ channels (LTCCs), mainly via CaV1.2, and we showed that this influx constitutes a necessary and sufficient signal for triggering the expression of neural genes. However, the mechanism linking the inhibition of BMP signalling with the activation of LTCCs remained unknown. Here, we demonstrate that the transient receptor potential canonical subfamily member 1, (Trpc1), is an intermediate between BMP receptor type II (BMPRII) and the CaV1.2 channel. We show that noggin induces a physical interaction between BMPRII and Trpc1 channels. This interaction leads to the activation of Trpc1 channels and to an influx of cations, which depolarizes the plasma membrane up to a threshold sufficient to activate Cav1.2. Together, our results demonstrate for the first time that during neural induction, Ca2+ entry through the CaV1.2 channel results from the noggin-induced interaction between Trpc1 and BMPRII.

scholarly journals The Na+/Ca2+ Exchanger Inhibitor, KB-R7943, Blocks a Nonselective Cation Channel Implicated in Chemosensory Transduction

2009 ◽  
Vol 101 (3) ◽  
pp. 1151-1159 ◽  
Author(s):  
A. Pezier ◽  
Y. V. Bobkov ◽  
B. W. Ache
Keyword(s):  
Transient Receptor Potential ◽  
Single Channel ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Dependent Manner ◽  
Open Probability ◽  
Olfactory Transduction ◽  
Voltage Dependent ◽  
Chemosensory Transduction ◽  
Transient Receptor

The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a nonselective sodium-gated cation (SGC) channel, a presumptive transient receptor potential (TRP)C channel homolog, plays a crucial role in olfactory transduction, at least in part by amplifying the primary transduction current. To better determine the functional role of the channel, it is important to selectively block the channel independently of other elements of the transduction cascade, causing us to search for specific pharmacological blockers of the SGC channel. Given evidence that the Na+/Ca2+ exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we studied this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both inside- and outside-out patch recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the channel open probability without changing single channel amplitude. KB-R7943 also reversibly and in a dose-dependent manner inhibited both the odorant-evoked discharge of lobster ORNs and the odorant-evoked whole cell current. Our findings strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely does so directly and not through its ability to block the Na+/Ca2+ exchanger.

Ca2+ pathway involved in the refilling of store sites in rat adrenal medullary cells

2009 ◽  
Vol 296 (4) ◽  
pp. C889-C899 ◽  
Author(s):  
Hidetada Matsuoka ◽  
Keita Harada ◽  
Tomoya Ikeda ◽  
Kouta Uetsuki ◽  
Takeyoshi Sata ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Outward Current ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Experimental Result ◽  
Intracellular Ca ◽  
Serca Pump ◽  
Potential Channels ◽  
Trpc1 Channels ◽  
Transient Receptor

It has been suggested that store-operated Ca2+ entry (SOC) facilitates catecholamine secretion and synthesis in bovine adrenal medullary (AM) cells. However, there has been no experimental result clearly showing that cation channel activity is enhanced by store Ca2+ depletion. Thus the present experiments were undertaken to address the issue of whether rat AM cells have SOC channels. Inhibition of the sarco(endo)plasmic reticulum Ca2+ (SERCA) pump resulted in a sustained increase in intracellular Ca2+ concentration ([Ca2+]i) in rat AM cells. This increase was completely suppressed by 2 mM Ni2+ but not by 100 μM D600. A bath application of Ni2+, but not D600, produced an outward current at −60 mV in rat AM cells, whereas exposure to a SERCA pump inhibitor did not affect either the whole cell current level or the Ni2+-induced outward current. The refilling of intracellular store sites was suppressed by the addition of Ni2+ to the perfusate. RT-PCR revealed that transcripts for transient receptor potential channels 1 (TRPC1) and 5 (TRPC5) were present in rat adrenal medullas. Immunocytochemistry showed that TRPC1 channels, which have been implicated in SOC in certain types of cells, were mainly localized in the endoplasmic reticulum (ER) and not in the plasma membrane, and that STIM1, a Ca2+ sensor in the ER, was not expressed in rat AM cells. On the basis of these results, we conclude that rat AM cells lack the SOC mechanism.

scholarly journals Structure of the human TRPM4 ion channel in a lipid nanodisc

Science ◽  
2017 ◽  
Vol 359 (6372) ◽  
pp. 228-232 ◽  
Author(s):  
Henriette E. Autzen ◽  
Alexander G. Myasnikov ◽  
Melody G. Campbell ◽  
Daniel Asarnow ◽  
David Julius ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Calcium Binding ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Dependent Manner ◽  
Calcium Binding Site ◽  
Voltage Dependent ◽  
Transient Receptor ◽  
Lipid Nanodiscs

Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage-dependent manner but, unlike many other TRP channels, is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3-angstrom resolution, as determined by single-particle cryo–electron microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium-binding site within the intracellular side of the S1-S4 domain. The structures correspond to two distinct closed states. Calcium binding induces conformational changes that likely prime the channel for voltage-dependent opening.

scholarly journals Bone morphogenetic protein 4 enhances canonical transient receptor potential expression, store-operated Ca2+ entry, and basal [Ca2+]i in rat distal pulmonary arterial smooth muscle cells

2010 ◽  
Vol 299 (6) ◽  
pp. C1370-C1378 ◽  
Author(s):  
Wenju Lu ◽  
Pixin Ran ◽  
Dandan Zhang ◽  
Ning Lai ◽  
Nanshan Zhong ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Pulmonary Vascular Remodeling ◽  
Canonical Transient Receptor Potential ◽  
Morphogenetic Protein ◽  
Mrna And Protein Expression ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle ◽  
Transient Receptor

Recent advances have identified an important role of bone morphogenetic protein 4 (BMP4) in pulmonary vascular remodeling, yet the underlying mechanisms remain largely unexplored. We have previously found that Ca2+ influx through store-operated calcium channels (SOCC), which are mainly thought to be composed of canonical transient receptor potential (TRPC) proteins, likely contribute to the pathogenic development of chronic hypoxic pulmonary hypertension. In this study, we investigated the effect of BMP4 on expression of TRPC and store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs). Real-time quantitative PCR and Western blotting revealed that treatment with BMP4 (50 ng/ml, 60 h) increased TRPC1, TRPC4, and TRPC6 mRNA and protein expression in growth-arrested rat distal PASMCs. Moreover, in comparison to vehicle control, cells treated with BMP4 also exhibited enhanced SOCE, and elevated basal intracellular calcium concentration ([Ca2+]i) as determined by fluorescent microscopy using the Ca2+ indicator Fura-2 AM. Perfusing cells with Ca2+-free Krebs-Ringer bicarbonate solution (KRBS) or KRBS containing SOCC antagonists SKF-96365 or NiCl2 attenuated the increases in basal [Ca2+]i caused by BMP4. Specific knockdown of BMP4 by small interference RNA significantly decreased the mRNA and protein expression of TRPC1, TRPC4, and TRPC6 and reduced SOCE and basal [Ca2+]i in serum-stimulated PASMCs. We conclude that BMP4 regulates calcium signaling in PASMCs likely via upregulation of TRPC expression, leading to enhanced SOCE and basal [Ca2+]i in PASMCs, and by this mechanism contributes to pulmonary vascular remodeling during pulmonary arterial hypertension.

scholarly journals Attenuation of Canonical Transient Receptor Potential-Like Channel 6 Expression Specifically Reduces the Diacylglycerol-Mediated Increase in Intracellular Calcium in Human Myometrial Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 406-416 ◽  
Author(s):  
Daesuk Chung ◽  
Yoon-Sun Kim ◽  
Jennifer N. Phillips ◽  
Aida Ulloa ◽  
Chun-Ying Ku ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Contractile Activity ◽  
Receptor Potential ◽  
Myometrial Cells ◽  
Canonical Transient Receptor Potential ◽  
Voltage Dependent ◽  
Transient Receptor ◽  
Entry Mechanism

Abstract An increase in intracellular Ca2+ ([Ca2+]i) as a result of release of Ca2+ from intracellular stores or influx of extracellular Ca2+ contributes to the regulation of smooth muscle contractile activity. Human uterine smooth muscle cells exhibit receptor-, store-, and diacylglycerol (OAG)-mediated extracellular Ca2+-dependent increases in [Ca2+]i (SRCE) and express canonical transient receptor potential-like channels (TRPC) mRNAs (predominantly TRPC1, -4, and -6) that have been implicated in SRCE. To determine the role of TRPC6 in human myometrial SRCE, short hairpin RNA constructs were designed that effectively targeted a TRPC6 mRNA reporter for degradation. One sequence was used to produce an adenovirus construct (TC6sh1). TC6sh1 reduced TRPC6 mRNA but not TRPC1, -3, -4, -5, or -7 mRNAs in PHM1-41 myometrial cells. Compared with uninfected cells or cells infected with empty vector, the increase in [Ca2+]i in response to OAG was specifically inhibited by TC6sh1, whereas SRCE responses elicited by either oxytocin or thapsigargin were not changed. Similar findings were observed in primary pregnant human myometrial cells. When PHM1-41 cells were activated by OAG in the absence of extracellular Na+, the increase in [Ca2+]i was partially reduced. Furthermore, pretreatment with nifedipine, an L-type calcium channel blocker, also partially reduced the OAG-induced [Ca2+]i increase. Similar effects were observed in primary human myometrial cells. These findings suggest that OAG activates channels containing TRPC6 in myometrial cells and that these channels act via both enhanced Na+ entry coupled to activation of voltage-dependent Ca2+ entry channels and a nifedipine-independent Ca2+ entry mechanism to promote elevation of intracellular Ca2+.

scholarly journals PIP2 Activates TRPV5 and Releases Its Inhibition by Intracellular Mg2+

2005 ◽  
Vol 126 (5) ◽  
pp. 439-451 ◽  
Author(s):  
Jason Lee ◽  
Seung-Kuy Cha ◽  
Tie-Jun Sun ◽  
Chou-Long Huang
Keyword(s):  
Phospholipase C ◽  
Conformational Change ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Selectivity Filter ◽  
Induced Voltage ◽  
Voltage Dependent ◽  
Transient Receptor

The transient receptor potential type V5 channel (TRPV5) is a Ca2+-selective TRP channel important for epithelial Ca2+ transport. Intracellular Mg2+ causes a fast voltage-dependent block of the TRPV5 channel by binding to the selectivity filter. Here, we report that intracellular Mg2+ binding to the selectivity filter of TRPV5 also causes a slower reversible conformational change leading to channel closure. We further report that PIP2 activates TRPV5. Activation of TRPV5 by PIP2 is independent of Mg2+. Yet, PIP2 decreases sensitivity of the channel to the Mg2+-induced slow inhibition. Mutation of aspartate-542, a critical Mg2+-binding site in the selectivity filter, abolishes Mg2+-induced slow inhibition. PIP2 has no effects on Mg2+-induced voltage-dependent block. Thus, PIP2 prevents the Mg2+-induced conformational change without affecting Mg2+ binding to the selectivity filter. Hydrolysis of PIP2 via receptor activation of phospholipase C sensitizes TRPV5 to the Mg2+-induced slow inhibition. These results provide a novel mechanism for regulation of TRP channels by phospholipase C–activating hormones via alteration of the sensitivity to intracellular Mg2+.

scholarly journals Electrophysiological Properties of Endogenous Single Ca2+ Activated Cl− Channels Induced by Local Ca2+ Entry in HEK293

2021 ◽  
Vol 22 (9) ◽  
pp. 4767
Author(s):  
Dmitrii Kolesnikov ◽  
Anastasiia Perevoznikova ◽  
Konstantin Gusev ◽  
Lyubov Glushankova ◽  
Elena Kaznacheyeva ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chloride Channels ◽  
Transmembrane Potential ◽  
Transient Receptor Potential ◽  
Single Channel ◽  
Receptor Potential ◽  
Patch Clamp Technique ◽  
Electrophysiological Properties ◽  
Trpc1 Channels ◽  
Transient Receptor

Microdomains formed by proteins of endoplasmic reticulum and plasma membrane play a key role in store-operated Ca2+ entry (SOCE). Ca2+ release through inositol 1,4,5-trisphosphate receptor (IP3R) and subsequent Ca2+ store depletion activate STIM (stromal interaction molecules) proteins, sensors of intraluminal Ca2+, which, in turn, open the Orai channels in plasma membrane. Downstream to this process could be activated TRPC (transient receptor potential-canonical) calcium permeable channels. Using single channel patch-clamp technique we found that a local Ca2+ entry through TRPC1 channels activated endogenous Ca2+-activated chloride channels (CaCCs) with properties similar to Anoctamin6 (TMEM16F). Our data suggest that their outward rectification is based on the dependence from membrane potential of both the channel conductance and the channel activity: (1) The conductance of active CaCCs highly depends on the transmembrane potential (from 3 pS at negative potentials till 60 pS at positive potentials); (2) their activity (NPo) is enhanced with increasing Ca2+ concentration and/or transmembrane potential, conversely lowering of intracellular Ca2+ concentration reduced the open state dwell time; (3) CaCC amplitude is only slightly increased by intracellular Ca2+ concentration. Experiments with Ca2+ buffering by EGTA or BAPTA suggest close local arrangement of functional CaCCs and TRPC1 channels. It is supposed that Ca2+-activated chloride channels are involved in Ca2+ entry microdomains.

Magnesium-dependent block of the light-activated and trp-dependent conductance in Drosophila photoreceptors

1995 ◽  
Vol 74 (6) ◽  
pp. 2590-2599 ◽  
Author(s):  
R. C. Hardie ◽  
M. H. Mojet
Keyword(s):  
Transient Receptor Potential ◽  
Single Channel ◽  
Noise Analysis ◽  
Physiological Role ◽  
Receptor Potential ◽  
Cell Voltage ◽  
Resting Potential ◽  
Fold Reduction ◽  
Voltage Dependent ◽  
Transient Receptor

1. The effect of Mg2+ on the light-sensitive conductance in Drosophila photoreceptors was examined with the use of whole cell voltage-clamp recordings from dissociated ommatidia. In wild type (WT) photoreceptors, at resting potential (-70 mV). Mgo2+ reduces response amplitude by up to approximately 4-fold in the presence of normal (1.5 mM) Cao2+ and by up to 20-fold in the absence of Cao2+. The Mg2+ concentration required for 50% maximum block (K1/2) was approximately 1 mM with 1.5 mM Cao2+ and approximately 280 microM in Ca(2+)-free Ringer. 2. The Mg2+ block was largely relieved in photoreceptors of the transient receptor potential mutant (trp): the maximum block being only approximately twofold with a K1/2 of approximately 4 mM in both Ca(2+)-free and 1.5 mM Cao2+. 3. The Mg2+ block in WT, but not in trp, was strongly voltage dependent, being relieved by both hyperpolarization and depolarization. The Mg2+ block in WT also resulted in slower response kinetics because of the associated decrease in Ca2+ influx. 4. Noise analysis indicates that, with normal Ca(zero)2+, the Mg2+ block in WT is associated with a approximately 10-fold reduction in effective single-channel conductance al resting potential. 5. The results support the hypothesis that the trp gene encodes a subunit of a light-sensitive channel, which is required for sensitivity to block by Mg2+. The concentration and voltage dependence of the Mg2+ block suggest it plays an important physiological role in determining the gain, kinetics, and signal-to-noise of transduction.

Differential expression and alternative splicing of TRP channel genes in smooth muscles

2001 ◽  
Vol 280 (5) ◽  
pp. C1184-C1192 ◽  
Author(s):  
Rebecca L. Walker ◽  
Joseph R. Hume ◽  
Burton Horowitz
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Splice Variants ◽  
Smooth Muscles ◽  
Receptor Potential ◽  
Full Length ◽  
Alternative Processing ◽  
Voltage Dependent ◽  
Transient Receptor ◽  
Trp Genes

Nonselective cation channels (NSCC) are targets of excitatory agonists in smooth muscle, representing the nonselective cation current I cat. Na+ influx through NSCC causes depolarizations and activates voltage-dependent Ca2+ channels, resulting in contraction. The molecular identity of I cat in smooth muscle has not been elucidated; however, products of the transient receptor potential (TRP) genes have characteristics similar to native I cat. We have determined the levels of TRP transcriptional expression in several murine and canine gastrointestinal and vascular smooth muscles and have analyzed the alternative processing of these transcripts. Of the seven TRP gene family members, transcripts for TRP4, TRP6, and TRP7 were detected in all murine and canine smooth muscle cell preparations. TRP3 was detected only in canine renal artery smooth muscle cells. The full-length cDNAs for TRP4, TRP6, and TRP7, as well as one splice variant of TRP4 and two splice variants of TRP7, were cloned from murine colonic smooth muscle. Quantitative RT-PCR determined the relative amounts of TRP4, TRP6, and TRP7 transcripts, as well as that of the splice variants, in several murine smooth muscles. TRP4 is the most highly expressed, while TRP6 and TRP7 are expressed at a lower level in the same tissues. Splice variants for TRP7, deleted for exons encoding amino acids including transmembrane segment S1, predominated in murine smooth muscles, while the full-length form of the transcript was expressed in canine smooth muscles.

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