Pfluegers Archiv/European Journal of Physiology 2014-12-01

Excitation of rat sympathetic neurons via M1 muscarinic receptors independently of Kv7 channels.

Isabella Salzer, Hend Gafar, Viola Gindl, Peter Mahlknecht, Helmut Drobny, Stefan Boehm

Index: Pflugers Arch. 466(12) , 2289-303, (2014)

Full Text: HTML

Abstract

The slow cholinergic transmission in autonomic ganglia is known to be mediated by an inhibition of Kv7 channels via M1 muscarinic acetylcholine receptors. However, in the present experiments using primary cultures of rat superior cervical ganglion neurons, the extent of depolarisation caused by the M1 receptor agonist oxotremorine M did not correlate with the extent of Kv7 channel inhibition in the very same neuron. This observation triggered a search for additional mechanisms. As the activation of M1 receptors leads to a boost in protein kinase C (PKC) activity in sympathetic neurons, various PKC enzymes were inhibited by different means. Interference with classical PKC isoforms led to reductions in depolarisations and in noradrenaline release elicited by oxotremorine M, but left the Kv7 channel inhibition by the muscarinic agonist unchanged. M1 receptor-induced depolarisations were also altered when extra- or intracellular Cl(-) concentrations were changed, as were depolarising responses to γ-aminobutyric acid. Depolarisations and noradrenaline release triggered by oxotremorine M were reduced by the non-selective Cl(-) channel blockers 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid and niflumic acid. Oxotremorine M induced slowly rising inward currents at negative membrane potentials that were blocked by inhibitors of Ca(2+)-activated Cl(-) and TMEM16A channels and attenuated by PKC inhibitors. These channel blockers also reduced oxotremorine M-evoked noradrenaline release. Together, these results reveal that slow cholinergic excitation of sympathetic neurons involves the activation of classical PKCs and of Ca(2+)-activated Cl(-) channels in addition to the well-known inhibition of Kv7 channels.


Related Compounds

Related Articles:

Structure-based drug design identifies polythiophenes as antiprion compounds.

2015-08-05

[Sci. Transl. Med. 7 , 299ra123, (2015)]

Ultra trace analysis of PAHs by designing simple injection of large amounts of analytes through the sample reconcentration on SPME fiber after magnetic solid phase extraction.

2016-01-15

[Talanta 147 , 59-62, (2015)]

Two bisthienylethene-Ir(III) complexes showing acid/base-induced structural transformation and on-off luminescence switching in solution.

2015-12-28

[Dalton Trans. 44 , 21008-15, (2015)]

Detailed compositional characterization of plastic waste pyrolysis oil by comprehensive two-dimensional gas-chromatography coupled to multiple detectors.

2014-09-12

[J. Chromatogr. A. 1359 , 237-46, (2014)]

Length-dependent conductance of oligothiophenes.

2014-07-23

[J. Am. Chem. Soc. 136(29) , 10486-92, (2014)]

More Articles...