The mammalian TRPC cation channels

Vázquez, Guillermo; Wedel, Barbara J.; Aziz, Omar; Trebak, Mohamed; Putney, James W.

doi:10.1016/j.bbamcr.2004.08.015

Cited by 307 publications

(284 citation statements)

References 132 publications

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“…2 channels, which belong to the larger superfamily of mammalian TRP channel-forming proteins, are among the most important neurotransmitter and hormone-regulated cation channels in nonexcitable cells (1,2). Physiologically, TRPC channels function as multifunctional calcium-permeable cation channels that can be activated through the phospholipase C (PLC) pathway.…”

Section: Canonical Transient Receptor Potential (Trpc)mentioning

confidence: 99%

Native TRPC7 Channel Activation by an Inositol Trisphosphate Receptor-dependent Mechanism

Vázquez

Bird

Mori

et al. 2006

Journal of Biological Chemistry

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In DT40 B lymphocytes, Canonical Transient Receptor Potential 7 (TRPC7) functions as a diacylglycerol-activated non-selective cation channel. However, previous work indicated that the non-store-operated Ca 2؉ entry in this cell type depends upon inositol trisphosphate receptors (IP 3 R). With the cell-attached configuration oleyl-acetyl-glycerol (OAG) induced single channel activity (75 pS) that was not observed in TRPC7 ؊/؊ DT40 cells were indistinguishable from one another and from wildtype cells. Thus, TRPC7 forms, or is part of, the channel underlying endogenous diacylglycerol-activated currents in DT40 B lymphocytes, and this activity of native TRPC7 requires IP 3 R. However, with conditions expected to produce greater expression levels, TRPC7 functioned independently of the presence of IP 3 R. This finding may serve to resolve previously conflicting reports from expression studies of TRPC channels. Canonical Transient Receptor Potential (TRPC)2 channels, which belong to the larger superfamily of mammalian TRP channel-forming proteins, are among the most important neurotransmitter and hormone-regulated cation channels in nonexcitable cells (1, 2). Physiologically, TRPC channels function as multifunctional calcium-permeable cation channels that can be activated through the phospholipase C (PLC) pathway. However, whether individual TRPC members function as store-operated Ca 2ϩ channels (whose activation is initiated by depletion of Ca 2ϩ stores) and/or non-store-operated Ca 2ϩ channels following PLC activation is still a matter of debate. Some of the confusion stems from the fact that, when heterologously expressed, their mode of regulation seems to be strongly dependent on cell type, expression level, or expression environment (discussed in Ref.3). TRPC7 for instance, a member of the TRPC3/6/7 subfamily, was originally shown to function as a PLC-regulated channel (4), presumably through PLC-derived diacylglycerol (DAG), but subsequent evidence indicated that it could also function as a store-operated Ca 2ϩ channel (5). Recent work from our laboratory demonstrated that these apparently contradictory findings likely resulted from differences in expression conditions (6). In an attempt to determine which of these two behaviors may correspond to the physiological function of native, endogenously expressed TRPC7, we recently utilized targeted homologous recombination to knock out TRPC7 in DT40 B lymphocytes. We found that knock out of TRPC7 did not significantly affect the store-operated calciumselective current I crac known to be expressed in these cells (7). Rather, in the avian B-cell line, TRPC7 appears to function as a PLC-regulated, DAG-activated non-selective cation channel. However, previous studies from this laboratory (8) and others (9, 10) showed that in DT40 cells non-store-operated Ca 2ϩ , receptor-regulated cation entry depends in some manner on inositol trisphosphate (IP 3 ) receptors, but the precise role of IP 3 receptors (IP 3 R) in this pathway has not been defined. Because a Ca 2ϩ -impermeable...

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Section: Canonical Transient Receptor Potential (Trpc)mentioning

confidence: 99%

Native TRPC7 Channel Activation by an Inositol Trisphosphate Receptor-dependent Mechanism

Vázquez

Bird

Mori

et al. 2006

Journal of Biological Chemistry

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“…In thalamic nuclei, activation of 5-HT 2 receptors stimulates GABA release from dendrites of interneurons with a novel mechanism of action: 5-HT effect involved PLC and an increase in intracellular Ca 2+ concentration that did not depend on Ca 2+ release from stores nor on membrane voltage-gated Ca 2+ channels, but was instead critically dependent on the TRPC4 channel [134], a membrane cation channel belonging to the recently discovered family of transient receptor potential (TRP) channels whose function, still largely unknown, seems to be either store-operated or receptor-operated Ca 2+ channels [182]. By increasing GABA release from dendrites of thalamic interneurons, 5-HT can strengthen local GABAergic inhibition and ultimately modulate thalamic processing of sensory signals [134].…”

Section: Modulation Of Gaba-mediated Transmissionmentioning

confidence: 99%

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

Ciranna

2006

272

170

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Abstract:The neurotransmitter serotonin (5-HT), widely distributed in the central nervous system (CNS), is involved in a large variety of physiological functions. In several brain regions 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a "classical" neurotransmitter. In some cases 5-HT is co-localized in the same nerve terminal with other neurotransmitters and reciprocal interactions take place. This review will focus on the modulatory action of 5-HT on the effects of glutamate and -amino-butyric acid (GABA), which are the principal neurotransmitters mediating respectively excitatory and inhibitory signals in the CNS. Examples of interaction at preand/or post-synaptic levels will be illustrated, as well as the receptors involved and their mechanisms of action. Finally, the physiological meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect to pathologies deriving from malfunctioning of serotonin system.

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“…Originally, members of the TRPC subfamily were thought to open predominantly through activation of phospholipase C subtype (PLC) and G-proteincoupled receptors (GPCR), which generate inositol (1, 4, 5) triphosphate and diacylglycerol (DAG). 24 In Drosophila, light activates rhodopsin (GPCR), which in turn activates PLC. However, it turned out that some TRP channels were also gated by DAG itself, which implies a broader functional role than receptor-activated Ca 2 þ entry channels.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells

Chae

Kim

et al. 2005

Int J Impot Res

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Hypercholesterolemia is a major risk factor for erectile dysfunction. To understand the mechanism(s) of hypercholesterolemia-induced erectile dysfunction, we studied the effect of lysophosphatidylcholine (LPC) on the membrane conductance of corporal smooth muscle cells. We used cultured human corporal smooth muscle cells. The intracelluar Ca 2 þ concentration ([Ca 2 þ ] i ) and the influx of divalent cation was monitored by the ratio of fura-2 fluorescence (F 340/380 ) and by the Mn 2 þ -induced quenching rate of fura-2, respectively. The LPC-induced membrane current was characterized by the whole-cell patch-clamp technique and the molecular identity of suspected channels was probed by RT-PCR. LPC (20 lM) induced a statistically significant increase in F 340/380 to 119.973.9% of initial control (n ¼ 6) in corporal smooth muscle cells. The addition of 20 lM LPC accelerated the quenching rate of F 360 by 59.5711.8% (n ¼ 5). LPC activated nonselective cationic current (I LPC ), similar to the known effects of phenylephrine in corporal myocytes. The size of I LPC at À60 mV was À55.376.3 pA (n ¼ 8). The transcript of transient receptor potential channel 6 (TRPC6) was detected in human corporal myocytes. We also found one splicing variant of TRPC6, TRPC6a. In conclusion, the present study suggests that the LPC, a major component of oxidized lowdensity lipoprotiens, increases calcium in corporal smooth muscle cells probably through activation of a TRPC6 channel and the increased [Ca 2 þ ] i by LPC via TRP channels is one of mechanisms for hypercholesterolemia-induced erectile dysfunction.

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The mammalian TRPC cation channels

Cited by 307 publications

References 132 publications

Native TRPC7 Channel Activation by an Inositol Trisphosphate Receptor-dependent Mechanism

Native TRPC7 Channel Activation by an Inositol Trisphosphate Receptor-dependent Mechanism

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells

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