Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Long-term desensitization of nicotinic acetylcholine receptors is regulated via protein kinase A-mediated phosphorylation.
Paradiso K, Brehm P.
???displayArticle.abstract???
During prolonged application of transmitter, ligand-gated ion channels enter a nonconducting desensitized state. Studies on Torpedo electroplax nicotinic acetylcholine (ACh) receptors have shown that entry into the desensitized state is accelerated by protein kinase A-dependent (PKA) receptor phosphorylation. To examine the effects of phosphorylation on desensitization of muscle-type ACh receptors, we expressed the frog embryonic receptor type in Xenopus oocytes. Treatment of embryonic muscle ACh receptors with 8-Br cAMP had no measurable effect on the rate of entry into a desensitized state, but it greatly accelerated the recovery from desensitization. Three complementary approaches to reduce the levels of receptor phosphorylation provided additional evidence for a role of PKA-dependent phosphorylation in rescuing receptors from long-term desensitization. Inactivation of the endogenous PKA activity by coexpression of an inhibitor protein, treatment of receptors with phosphatase, and removal of phosphorylation sites by site-specific subunit mutation all resulted in slowed recovery. Our findings point to the existence of two distinct desensitized states: one requiring several seconds for full recovery and a second state from which recovery requires minutes. Receptors lacking PKA phosphorylation sites exhibit a pronounced increase in the slowly recovering component of desensitization, suggesting that receptor phosphorylation speeds overall recovery by reducing the entry into a deep desensitized state. This newly described effect of phosphorylation on ACh receptor function may serve as an important modulator of postsynaptic receptor sensitivity.
Auerbach,
Activation of the primary kinetic modes of large- and small-conductance cholinergic ion channels in Xenopus myocytes.
1987, Pubmed,
Xenbase
Auerbach,
Activation of the primary kinetic modes of large- and small-conductance cholinergic ion channels in Xenopus myocytes.
1987,
Pubmed
,
Xenbase Boyd,
Two distinct kinetic phases of desensitization of acetylcholine receptors of clonal rat PC12 cells.
1987,
Pubmed Cachelin,
Desensitization of the acetylcholine receptor of frog end-plates measured in a Vaseline-gap voltage clamp.
1989,
Pubmed Camacho,
The epsilon subunit confers fast channel gating on multiple classes of acetylcholine receptors.
1993,
Pubmed
,
Xenbase Charnet,
Structure of the gamma-less nicotinic acetylcholine receptor: learning from omission.
1992,
Pubmed
,
Xenbase Colquhoun,
From muscle endplate to brain synapses: a short history of synapses and agonist-activated ion channels.
1998,
Pubmed Dilger,
Desensitization of acetylcholine receptors in BC3H-1 cells.
1992,
Pubmed FATT,
The electromotive action of acetylcholine at the motor end-plate.
1950,
Pubmed Feltz,
Desensitization at the frog neuromuscular junction: a biphasic process.
1982,
Pubmed Franke,
Steep concentration dependence and fast desensitization of nicotinic channel currents elicited by acetylcholine pulses, studied in adult vertebrate muscle.
1991,
Pubmed Franke,
Activation and desensitization of embryonic-like receptor channels in mouse muscle by acetylcholine concentration steps.
1992,
Pubmed Fu,
Potentiation of acetylcholine responses in Xenopus embryonic muscle cells by dibutyryl cAMP.
1993,
Pubmed
,
Xenbase Greengard,
Enhancement of the glutamate response by cAMP-dependent protein kinase in hippocampal neurons.
1991,
Pubmed Hoffman,
Role of phosphorylation in desensitization of acetylcholine receptors expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase Hopfield,
Functional modulation of the nicotinic acetylcholine receptor by tyrosine phosphorylation.
1988,
Pubmed Huganir,
Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization.
,
Pubmed Huganir,
Regulation of neurotransmitter receptor desensitization by protein phosphorylation.
1990,
Pubmed Jackson,
Spontaneous and agonist-induced openings of an acetylcholine receptor channel composed of bovine muscle alpha-, beta- and delta-subunits.
1990,
Pubmed
,
Xenbase Jones,
The impact of receptor desensitization on fast synaptic transmission.
1996,
Pubmed KATZ,
A study of the desensitization produced by acetylcholine at the motor end-plate.
1957,
Pubmed Kullberg,
Multiple conductance classes of mouse nicotinic acetylcholine receptors expressed in Xenopus oocytes.
1990,
Pubmed
,
Xenbase Liu,
Expression of subunit-omitted mouse nicotinic acetylcholine receptors in Xenopus laevis oocytes.
1993,
Pubmed
,
Xenbase Lu,
Calcitonin gene-related peptide potentiates synaptic responses at developing neuromuscular junction.
1993,
Pubmed
,
Xenbase Magleby,
A study of desensitization of acetylcholine receptors using nerve-released transmitter in the frog.
1981,
Pubmed Margiotta,
Cyclic AMP regulates the proportion of functional acetylcholine receptors on chicken ciliary ganglion neurons.
1987,
Pubmed McDonald,
Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMP-dependent protein kinase.
1998,
Pubmed Middleton,
Desensitization of acetylcholine receptors in rat myotubes is enhanced by agents that elevate intracellular cAMP.
1988,
Pubmed Miles,
Calcitonin gene-related peptide regulates phosphorylation of the nicotinic acetylcholine receptor in rat myotubes.
1989,
Pubmed Murray,
A single site on the epsilon subunit is responsible for the change in ACh receptor channel conductance during skeletal muscle development.
1995,
Pubmed
,
Xenbase Naranjo,
Modal shifts in acetylcholine receptor channel gating confer subunit-dependent desensitization.
1993,
Pubmed
,
Xenbase Pennefather,
Fast desensitization of the nicotinic receptor at the mouse neuromuscular junction.
1982,
Pubmed Raman,
Beta-adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase.
1996,
Pubmed Raman,
The mechanism of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor desensitization after removal of glutamate.
1995,
Pubmed Ruzzier,
The effect of repetitive neuromuscular activity on the sensitivity of acetylcholine receptors.
1986,
Pubmed THESLEFT,
The mode of neuromuscular block caused by acetylcholine, nicotine, decamethonium and succinylcholine.
1955,
Pubmed Tong,
Synaptic desensitization of NMDA receptors by calcineurin.
1995,
Pubmed Vijayaraghavan,
Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit.
1990,
Pubmed Zorumski,
Properties of vertebrate glutamate receptors: calcium mobilization and desensitization.
1992,
Pubmed
