Canonical transient receptor potential channel 2 (TRPC2): old name-new games. Importance in regulating of rat thyroid cell physiology.

In addition to the TSH-cyclic AMP signalling pathway, calcium signalling is of crucial importance in thyroid cells. Although the importance of calcium signalling has been thoroughly investigated for several decades, the nature of the calcium channels involved in signalling is unknown. In a recent series of investigations using the well-studied rat thyroid FRTL-5 cell line, we showed that these cells exclusively express the transient receptor potential canonical 2 (TRPC2) channel.

Significance of the transient receptor potential canonical 2 (TRPC2) channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion.

Mammalian transient receptor potential (TRP) channels are involved in many physiologically important processes. Here, we have studied the significance of the TRPC2 channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion, using stable TRPC2 (shTRPC2) knock-down cells. In the shTRPC2 cells, proliferation was decreased due to a prolonged G1/S cell cycle phase.

Canonical transient receptor potential channel 2 (TRPC2) as a major regulator of calcium homeostasis in rat thyroid FRTL-5 cells: importance of protein kinase C δ (PKCδ) and stromal interaction molecule 2 (STIM2).

Mammalian non-selective transient receptor potential cation channels (TRPCs) are important in the regulation of cellular calcium homeostasis. In thyroid cells, including rat thyroid FRTL-5 cells, calcium regulates a multitude of processes. RT-PCR screening of FRTL-5 cells revealed the presence of TRPC2 channels only.

Functional coupling of TRPC2 cation channels and the calcium-activated anion channels in rat thyroid cells: implications for iodide homeostasis.

The initial step in a synthesis of thyroid hormones is the uptake of iodide from the circulation. Iodide (I(-)) is transported into thyroid cells via a Na(+)/I(-) symporter (NIS), which is electrogenic and thus sensitive to alterations in membrane potential (V(m)). I(-) is then released to the lumen of thyroid follicles where the hormones are synthesised and stored.

Communication between the calcium and cAMP pathways regulate the expression of the TSH receptor: TRPC2 in the center of action.

Transient receptor potential (TRP) cation channels are widely expressed and function in many physiologically important processes. Perturbations in the expression or mutations of the channels have implications for diseases. Many thyroid disorders, as excessive growth or disturbed thyroid hormone production, can be a result of dysregulated TSH signaling.

Sphingosine 1-phosphate and human ether-a'-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells.

Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a'-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P(1-3) receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level.

TRPC2: of mice but not men.

Relatively little is known in regard to the physiological significance of TRPC2 and its regulation or interaction with other calcium regulating signalling molecules. In rodents, however, the importance of TRPC2 is indisputable. In mice, transcripts for TRPC2 have been found in testis, sperm, in neurons in the vomeronasal organ, and both in the dorsal root ganglion and in the brain.

The K+-Cl cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus.

GABAergic excitatory [K(+)](o) transients can be readily evoked in the mature rat hippocampus by intense activation of GABA(A) receptors (GABA(A)Rs). Here we show that these [K(+)](o) responses induced by high-frequency stimulation or GABA(A) agonist application are generated by the neuronal K(+)-Cl() cotransporter KCC2 and that the transporter-mediated KCl extrusion is critically dependent on the bicarbonate-driven accumulation of Cl() in pyramidal neurons. The mechanism underlying GABAergic [K(+)](o) transients was studied in CA1 stratum pyramidale using intracellular sharp microelectrodes and extracellular ion-sensitive microelectrodes.

Regulation of HERG (KCNH2) potassium channel surface expression by diacylglycerol.

The HERG (KCNH2) channel is a voltage-sensitive potassium channel mainly expressed in cardiac tissue, but has also been identified in other tissues like neuronal and smooth muscle tissue, and in various tumours and tumour cell lines. The function of HERG has been extensively studied, but it is still not clear what mechanisms regulate the surface expression of the channel. In the present report, using human embryonic kidney cells stably expressing HERG, we show that diacylglycerol potently inhibits the HERG current.

Expression and significance of HERG (KCNH2) potassium channels in the regulation of MDA-MB-435S melanoma cell proliferation and migration.

The human ether-a-go-go related gene (HERG) potassium channel has elicited intense scientific interest due to its role in cardiac repolarization and its association with arrhythmia and sudden cardiac death. Increasing evidence indicates the involvement of HERG channels in the pathophysiology of cancer. In the present study we investigated the expression of HERG protein in MDA-MB-435S melanoma cells, and its importance in regulating cell proliferation and migration.

Cell type-specific differences in chloride-regulatory mechanisms and GABA(A) receptor-mediated inhibition in rat substantia nigra.

The regulation of intracellular chloride has important roles in neuronal function, especially by setting the magnitude and direction of the Cl- flux gated by GABA(A) receptors. Previous studies have shown that GABA(A)-mediated inhibition is less effective in dopaminergic than in GABAergic neurons in substantia nigra. We studied whether this phenomenon may be related to a difference in Cl-regulatory mechanisms.

BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion.

Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl- regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+-Cl- cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl- extrusion capacity.