α1-adrenoceptor-mediated depolarization and β-mediated hyperpolarization in cultured rat dorsal root ganglion neurones

Pluteanu, Florentina; Ristoiu, Violeta; Flonta, Maria-Luiza; Reid, Gordon

doi:10.1016/s0304-3940(02)00665-1

Cited by 31 publications

(19 citation statements)

References 18 publications

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“…The resting membrane potential of DRG neurons is ϳϪ60 mV (27,34). This negative resting membrane potential is likely to be the net effect of both the inward current via the nonselective cation channels and the larger outward current via K ϩ channels.…”

Section: Discussionmentioning

confidence: 99%

TREK-2 (K_2P10.1) and TRESK (K_2P18.1) are major background K⁺ channels in dorsal root ganglion neurons

Kang¹,

Kim²

2006

American Journal of Physiology-Cell Physiology

187

221

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Dorsal root ganglion (DRG) neurons express mRNAs for many two-pore domain K(+) (K(2P)) channels that behave as background K(+) channels. To identify functional background K(+) channels in DRG neurons, we examined the properties of single-channel openings from cell-attached and inside-out patches from the cell bodies of DRG neurons. We found seven types of K(+) channels, with single-channel conductance ranging from 14 to 120 pS in 150 mM KCl bath solution. Four of these K(+) channels showed biophysical and pharmacological properties similar to TRESK (14 pS), TREK-1 (112 pS), TREK-2 (50 pS), and TRAAK (73 pS), which are members of the K(2P) channel family. The molecular identity of the three other K(+) channels could not be determined, as they showed low channel activity and were observed infrequently. Of the four K(2P) channels, the TRESK-like (14 pS) K(+) channel was most active at 24 degrees C. At 37 degrees C, the 50-pS (TREK-2 like) channel was the most active and contributed the most (69%) to the resting K(+) current, followed by the TRESK-like 14-pS (16%), TREK-1-like 112-pS (12%), and TRAAK-like 73-pS (3%) channels. In DRG neurons, mRNAs of all four K(2P) channels, as well as those of TASK-1 and TASK-3, were expressed, as judged by RT-PCR analysis. Our results show that TREKs and TRESK together contribute >95% of the background K(+) conductance of DRG neurons at 37 degrees C. As TREKs and TRESK are targets of modulation by receptor agonists, they are likely to play an active role in the regulation of excitability in DRG neurons.

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Section: Discussionmentioning

confidence: 99%

TREK-2 (K_2P10.1) and TRESK (K_2P18.1) are major background K⁺ channels in dorsal root ganglion neurons

Kang¹,

Kim²

2006

American Journal of Physiology-Cell Physiology

187

221

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“…In animal models of peripheral nerve lesions, sympathetic nerve sprouting was also detected in the dorsal root ganglia (DRG) and these sympathetic fibers formed baskets around large primary neuronal cell bodies (Gibbs et al 2008;McLachlan et al, 1993;Pertovaara, 2006), of non-nociceptive A-fibers (Michaelis et al, 1996). In cultured DRG neurons, α 1 -adrenoceptor stimulation increases cell excitability, whereas β-adrenergic stimulation reduces it (Pluteanu et al, 2002). However, the clinical relevance of that observation has to be proven because Häbler et al found sympatheticsensory coupling only in a minority of axotomized afferents after spinal nerve injury using…”

Section: The Impact Of the Sns On Neurogenic Inflammation In Crpsmentioning

confidence: 99%

Inflammation in CRPS: Role of the sympathetic supply

Schlereth

Drummond

Birklein

2014

Autonomic Neuroscience

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Acute Complex regional Pain Syndrome (CRPS) is associated with signs of inflammation such as increased skin temperature, edema, skin colour changes and pain. Pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-1beta, IL-6) are up-regulated, whereas anti-inflammatory cytokines (IL-4, IL-10) are diminished. Adaptive immunity seems to be involved in CRPS pathophysiology as many patients have autoantibodies directed against β 2 adrenergic and muscarinic-2 receptors. In an animal tibial fracture model changes in the innate immune response such as up-regulation of keratinocytes are also found. Additionally, CRPS is accompanied by increased neurogenic inflammation which depends mainly on neuropeptides such as CGRP and Substance P.Besides inflammatory signs, sympathetic nervous system involvement in CRPS results in cool skin, increased sweating and sympathetically-maintained pain. The norepinephrine level is lower in the CRPS-affected than contralateral limb, but sympathetic sprouting and up-regulation of alphaadrenoceptors may result in an adrenergic supersensitivity.The sympathetic nervous system and inflammation interact: norepinephrine influences the immune system and the production of cytokines. There is substantial evidence that this interaction contributes to the pathophysiology and clinical presentation of CRPS, but this interaction is not straightforward. How inflammation in CRPS might be exaggerated by sympathetic transmitters requires further elucidation.

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“…Extracellular recording studies in the VMN show that in vivo exposure to estradiol increases the responsiveness to norepinephrine and facilitates excitatory responses mediated by ␣ 1 -adrenoceptors (5,12,13). The ␣ 1 -adrenergic agonist phenylephrine (PHE) increases neuronal excitability in several other brain regions, including the substantia nigra pars reticulata (14) and lateral septum (15), and the dorsal root ganglion (16).…”

mentioning

confidence: 99%

Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats

Lee

Kyrozis

Chevaleyre

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatment in vivo induces ␣1b-adrenoreceptor mRNA and increases the density of ␣1B-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic ␣1-adrenoceptors also facilitates estrogen-dependent lordosis. To investigate the cellular mechanisms of adrenergic effects on VMN neurons, whole-cell patch-clamp recordings were carried out on hypothalamic slices from control and estradiol-treated female rats. In control slices, bath application of the ␣1-agonist phenylephrine (PHE; 10 M) depolarized 10 of 25 neurons (40%), hyperpolarized three neurons (12%), and had no effect on 12 neurons (48%). The depolarization was associated with decreased membrane conductance, and this current had a reversal potential close to the K ؉ equilibrium potential. The ␣ 1b -receptor antagonist chloroethylclonidine (10 M) blocked the depolarization produced by PHE in all cells. From estradiol-treated rats, significantly more neurons in slices depolarized (71%) and fewer neurons showed no response (17%) to PHE. PHEinduced depolarizations were significantly attenuated with 4-aminopyridine (5 mM) but unaffected by tetraethylammonium chloride (20 mM) or blockers of Na ؉ and Ca 2؉ channels. These data indicate that ␣1-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K ؉ . Estradiol amplifies ␣1b-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of ␣1b-adrenergic receptors, which is expected in turn to promote lordosis.estrogen ͉ norepinephrine ͉ ventromedial hypothalamus T he ventromedial nucleus of the hypothalamus (VMN) has estrogen-concentrating neurons and is known for its role in the expression of female sexual behavior (1). Estrogens act within in the ventrolateral portion of the VMN to facilitate female reproductive behavior. Estradiol treatment in vivo increases levels of mRNA encoding the ␣ 1b -adrenergic receptor and decreases levels of ␣ 2 -adrenergic receptor protein and mRNA (2, 3). ␣ 1 -Adrenergic transmission facilitates estrogendependent sexual behavior in rodents (4, 5). One brain area where norepinephrine is thought to have this effect is in the VMN. The VMN is innervated by noradrenergic nerve terminals that originate from the brainstem A1 and A2 cell groups (6).There is a considerable amount of evidence that noradrenergic inputs to the hypothalamus are involved in the neuroendocrine control of female reproductive behavior: (i) neurotoxininduced lesions of hypothalamic noradrenergic terminals impair lordosis behavior in ovariectomized, estrogen/progesteronetreated female rats (7), (ii) microinjection of norepinephrine or adrenergic receptor agonists directly into the VMN induces lordosis in ovariectomized, estrogen-primed female rats (8), (iii) implantation of the ␣ 1 -noradrenergic receptor antagonist prazosin into the ventrolateral VMN of ovariectomized, steroid primed rats inhibits lordosis (9), (iv) norepinephrine is released with...

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α1-adrenoceptor-mediated depolarization and β-mediated hyperpolarization in cultured rat dorsal root ganglion neurones

Cited by 31 publications

References 18 publications

TREK-2 (K_2P10.1) and TRESK (K_2P18.1) are major background K⁺ channels in dorsal root ganglion neurons

TREK-2 (K_2P10.1) and TRESK (K_2P18.1) are major background K⁺ channels in dorsal root ganglion neurons

Inflammation in CRPS: Role of the sympathetic supply

Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats

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α1-adrenoceptor-mediated depolarization and β-mediated hyperpolarization in cultured rat dorsal root ganglion neurones

Cited by 31 publications

References 18 publications

TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons

TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons

Inflammation in CRPS: Role of the sympathetic supply

Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats

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Product

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TREK-2 (K_2P10.1) and TRESK (K_2P18.1) are major background K⁺ channels in dorsal root ganglion neurons

TREK-2 (K_2P10.1) and TRESK (K_2P18.1) are major background K⁺ channels in dorsal root ganglion neurons