Inhibition of human TREK-1 channels by caffeine and theophylline

Harinath, S.; Sikdar, Sujit Kumar

doi:10.1016/j.eplepsyres.2005.03.002

Cited by 17 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of seizures is, however, still unclear. Most relevant to the pharmacological and toxicological effects of caffeine are (1) the blockade of adenosine receptors, (2) the inhibition of cyclic nucleotide phosphodiesterases, (3) the sensitization to calcium of the cyclic adenosine diphosphate ribose-modulated calcium-release channel associated with certain intracellular stores of calcium, (4) the inhibition of inhibitory GABA-A and glycine receptors, and (5) the enhancement of N-methyl-D-aspartic acid (NMDA) receptor neurotransmission (Daly, 2000;Harinath and Sikdar, 2005). As shown in Fig.2 and Table 2, in the caffeine model, although amiodarone had no effect on the convulsion rates and the mortality, it had prolonged the latency time and the time to death; amiodarone was more effective in the PTZ model than in the caffeine model.…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant and hypnotic effects of amiodarone

Özbakış-Dengiz

Bakirci²

2009

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Amiodarone hydrochloride is a potent anti-arrhythmic agent, known as a multiple ion-channel blocker in the heart. Although it has been detected in the rat brain, there are no data related to its central nervous system (CNS) effects. In this study, we evaluated anticonvulsant and hypnotic effects of amiodarone. Convulsions were induced by phentylenetetrazole (PTZ) (100 mg/kg) or caffeine (300 mg/kg) in mice. In both models, amiodarone prolonged both latency period and time to death, and acted as an anticonvulsant drug. It was found to be more effective in the PTZ model than in the caffeine model; none of the animals treated with 150 mg/kg dose amiodarone had died in the PTZ model. For hypnotic effect, sleeping was induced with pentobarbital (35 mg/kg) in rats. Amiodarone dose-dependently increased the sleeping time (677.7%~725.9%). In the sleeping test, all rats in 200 mg/kg amiodarone group died. In conclusion, anticonvulsant and hypnotic effects of amiodarone have shown the depressant effects on CNS. These effects may be dependent on its pharmacological properties.

show abstract

Section: Discussionmentioning

confidence: 99%

Anticonvulsant and hypnotic effects of amiodarone

Özbakış-Dengiz

Bakirci²

2009

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

show abstract

“…The actions of caffeine include the release of calcium from intracellular stores (14,64), inhibition of phosphodiesterase (PDE) (46,63), and antagonism of adenosine receptors (51). It has also been demonstrated that caffeine at high concentrations acts as an inhibitor of several potassium channels, including depolarization-activated potassium channels in sympathetic neurons, secretory cells (59), taste receptor cells (93), and ventricular myocytes (67); calciumactivated potassium (K Ca ) channels in GH 3 pituitary cells (41), sympathetic neurons (59), secretory cells (59), vascular smooth muscle cells (54), and taste receptor cells (93); human ether a-go-go-related gene potassium (hERG) channels in transfected mammalian cells (17); Kir channels in GH 3 rat anterior pituitary cells (9), ventricular myocytes (15,67,85), and taste receptor cells (93); K ATP channels in pancreatic ␤-cells (36) and smooth muscle cells (80); and recombinant two-pore domain potassium channel TREK-1 in Chinese hamster ovary (CHO) cells (26). On the other hand, caffeine has also been shown to increase potassium efflux in skeletal muscle (86) and to activate K Ca channels in adrenal chromaffin cells (55).…”

mentioning

confidence: 99%

Dual regulation of the ATP-sensitive potassium channel by caffeine

Mao¹,

Chai²,

Lin³

2007

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

ATP-sensitive potassium (K(ATP)) channels couple cellular metabolic status to changes in membrane electrical properties. Caffeine (1,2,7-trimethylxanthine) has been shown to inhibit several ion channels; however, how caffeine regulates K(ATP) channels was not well understood. By performing single-channel recordings in the cell-attached configuration, we found that bath application of caffeine significantly enhanced the currents of Kir6.2/SUR1 channels, a neuronal/pancreatic K(ATP) channel isoform, expressed in transfected human embryonic kidney (HEK)293 cells in a concentration-dependent manner. Application of nonselective and selective phosphodiesterase (PDE) inhibitors led to significant enhancement of Kir6.2/SUR1 channel currents. Moreover, the stimulatory action of caffeine was significantly attenuated by KT5823, a specific PKG inhibitor, and, to a weaker extent, by BAPTA/AM, a membrane-permeable Ca(2+) chelator, but not by H-89, a selective PKA inhibitor. Furthermore, the stimulatory effect was completely abrogated when KT5823 and BAPTA/AM were co-applied with caffeine. In contrast, the activity of Kir6.2/SUR1 channels was decreased rather than increased by caffeine in cell-free inside-out patches, while tetrameric Kir6.2LRKR368/369/370/371AAAA channels were suppressed regardless of patch configurations. Caffeine also enhanced the single-channel currents of recombinant Kir6.2/SUR2B channels, a nonvascular smooth muscle K(ATP) channel isoform, although the increase was smaller. Moreover, bidirectional effects of caffeine were reproduced on the K(ATP) channel present in the Cambridge rat insulinoma G1 (CRI-G1) cell line. Taken together, our data suggest that caffeine exerts dual regulation on the function of K(ATP) channels: an inhibitory regulation that acts directly on Kir6.2 or some closely associated regulatory protein(s), and a sulfonylurea receptor (SUR)-dependent stimulatory regulation that requires cGMP-PKG and intracellular Ca(2+)-dependent signaling.

show abstract

“…In addition to activation by mechanical stretch, K 2P 2.1 opens in response to high temperatures (6), lysophospholipids (7), internal acidosis (8), arachidonic acid (9), volatile general anesthetics (10), and other agents. K 2P 2.1 activity is down-regulated upon phosphorylation by protein kinases A and C (2) and inhibited by various compounds such as fluoxetine (Prozac) (12), caffeine, and theophylline (13). It has been suggested that K 2P 2.1 is an important target for volatile anesthetics and participates in protection against epilepsy and neuroprotection during brain and spinal chord ischemia (14).…”

mentioning

confidence: 99%

A Novel Mechanism for Human K2P2.1 Channel Gating

Golan‐Cohen

Ben-Abu

Hen

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

The mammalian K 2P 2.1 potassium channel (TREK-1, KCNK2) is highly expressed in excitable tissues, where it plays a key role in the cellular mechanisms of neuroprotection, anesthesia, pain perception, and depression. Here, we report that external acidification, within the physiological range, strongly inhibits the human K 2P 2.1 channel by inducing "C-type" closure. We have identified two histidine residues (i.e. His-87 and His-141), located in the first external loop of the channel, that govern the response of the channel to external pH. We demonstrate that these residues are within physical proximity to glutamate 84, homologous to Shaker Glu-418, KcsA Glu-51, and KCNK0 Glu-28 residues, all previously argued to stabilize the outer pore gate in the open conformation by forming hydrogen bonds with poreadjacent residues. We thus propose a novel mechanism for pH sensing in which protonation of His-141 and His-87 generates a local positive charge that serves to draw Glu-84 away from its natural interactions, facilitating the collapse of the selectivity filter region. In accordance with this proposed mechanism, low pH modified K 2P 2.1 selectivity toward potassium. Moreover, the proton-mediated effect was inhibited by external potassium ions and was enhanced by a mutation (S164Y) known to accelerate C-type gating. Furthermore, proton-induced current inhibition was more pronounced at negative potentials. Thus, voltage-dependent C-type gating acceleration by protons represents a novel mechanism for K 2P 2.1 outward rectification.

show abstract

Inhibition of human TREK-1 channels by caffeine and theophylline

Cited by 17 publications

References 38 publications

Anticonvulsant and hypnotic effects of amiodarone

Anticonvulsant and hypnotic effects of amiodarone

Dual regulation of the ATP-sensitive potassium channel by caffeine

A Novel Mechanism for Human K2P2.1 Channel Gating

Contact Info

Product

Resources

About