Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neurons

Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium... Melanin‐concentrating hormone (MCH), a cyclic 19‐amino‐acid peptide, is synthesized exclusively by neurons in the lateral hypothalamic (LH) area. It is involved in a number of brain functions and recently has raised interest because of its role in energy homeostasis. MCH axons and receptors are found throughout the brain. Previous reports set the foundation for understanding the cellular actions of MCH by using non‐neuronal cells transfected with the MCH receptor gene; these cells exhibited an increase in cytoplasmic calcium in response to MCH, suggesting an excitatory action for the peptide. In the study presented here, we have used whole‐cell recording in 117 neurons from LH cultures and brain slices to examine the actions of MCH. MCH decreased the amplitude of voltage‐dependent calcium currents in almost all tested neurons. The inhibition desensitized rapidly (18 s to half maximum at 100 nm concentration) and was dose‐dependent (IC50= 7.8 nm) when activated with a pulse from –80 mV to 0 mV. A priori activation of G‐proteins with GTPγS completely eliminated the MCH‐induced effect at low MCH concentrations and reduced the MCH‐induced effect at high MCH concentrations. Inhibition of G‐proteins with pertussis toxin (PTX) blocked the MCH‐induced inhibitory effect at high MCH concentrations. Pre‐pulse depolarization resulted in an attenuation of the MCH‐induced inhibition of calcium currents in most neurons. These data suggest that MCH exerts an inhibitory effect on calcium currents via PTX‐sensitive G‐protein pathways, probably the Gi/Go pathway, in LH neurons. L‐, N‐ and P/Q‐type calcium channels were identified in LH neurons, with L‐ and N‐type channels accounting for most of the voltage‐activated current (about 40 % each); MCH attenuated each of the three types (mean 50 % depression), with the greatest inhibition found for N‐type currents. In contrast to previous data on non‐neuronal cells showing an MHC‐evoked increase in calcium, our data suggest that the reverse occurs in LH neurons. The attenuation of calcium currents is consistent with an inhibitory action for the peptide in neurons. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Physiology Wiley

Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neurons

Loading next page...
 
/lp/wiley/melanin-concentrating-hormone-depresses-l-n-and-p-q-type-voltage-of1MhrjWYS
Publisher
Wiley
Copyright
Copyright © 2002 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3751
eISSN
1469-7793
DOI
10.1113/jphysiol.2002.019372
Publisher site
See Article on Publisher Site

Abstract

Melanin‐concentrating hormone (MCH), a cyclic 19‐amino‐acid peptide, is synthesized exclusively by neurons in the lateral hypothalamic (LH) area. It is involved in a number of brain functions and recently has raised interest because of its role in energy homeostasis. MCH axons and receptors are found throughout the brain. Previous reports set the foundation for understanding the cellular actions of MCH by using non‐neuronal cells transfected with the MCH receptor gene; these cells exhibited an increase in cytoplasmic calcium in response to MCH, suggesting an excitatory action for the peptide. In the study presented here, we have used whole‐cell recording in 117 neurons from LH cultures and brain slices to examine the actions of MCH. MCH decreased the amplitude of voltage‐dependent calcium currents in almost all tested neurons. The inhibition desensitized rapidly (18 s to half maximum at 100 nm concentration) and was dose‐dependent (IC50= 7.8 nm) when activated with a pulse from –80 mV to 0 mV. A priori activation of G‐proteins with GTPγS completely eliminated the MCH‐induced effect at low MCH concentrations and reduced the MCH‐induced effect at high MCH concentrations. Inhibition of G‐proteins with pertussis toxin (PTX) blocked the MCH‐induced inhibitory effect at high MCH concentrations. Pre‐pulse depolarization resulted in an attenuation of the MCH‐induced inhibition of calcium currents in most neurons. These data suggest that MCH exerts an inhibitory effect on calcium currents via PTX‐sensitive G‐protein pathways, probably the Gi/Go pathway, in LH neurons. L‐, N‐ and P/Q‐type calcium channels were identified in LH neurons, with L‐ and N‐type channels accounting for most of the voltage‐activated current (about 40 % each); MCH attenuated each of the three types (mean 50 % depression), with the greatest inhibition found for N‐type currents. In contrast to previous data on non‐neuronal cells showing an MHC‐evoked increase in calcium, our data suggest that the reverse occurs in LH neurons. The attenuation of calcium currents is consistent with an inhibitory action for the peptide in neurons.

Journal

The Journal of PhysiologyWiley

Published: Jul 1, 2002

References

  • Investigations into neuropeptide Y‐mediated presynaptic inhibition in cultured hippocampal neurones of the rat
    Bleakman, Bleakman; Harrison, Harrison; Colmers, Colmers; Miller, Miller
  • Calcium controls the transcription of its own transporters and channels in developing neurons
    Carafoli, Carafoli; Genassani, Genassani; Guerini, Guerini
  • Neurotrophin‐3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the rat
    Gao, Gao; Pol, Pol
  • Melanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamus
    Gao, Gao; Pol, Pol
  • The cyclic AMP‐dependent protein kinase catalytic subunit selectively enhances calcium currents in rat nodose neurones
    Gross, Gross; Uhler, Uhler; MacDonald, MacDonald
  • Melanin‐concentrating hormone (MCH) modifies memory retention in rats
    Monzon, Monzon; Souza, Souza; Izquierdo, Izquierdo; Izquierdo, Izquierdo; Barros, Barros; De Barioglio, De Barioglio
  • Cloning of a novel g protein‐coupled receptor, slt, a subtype of the melanin‐concentrating hormone receptor
    Mori, Mori; Harada, Harada; Terao, Terao; Sugo, Sugo; Watanabe, Watanabe; Shimomura, Shimomura; Abe, Abe; Shintani, Shintani; Onda, Onda; Nishimura, Nishimura; Fujino, Fujino
  • Nociceptin receptor‐mediated Ca 2+ channel inhibition and its desensitization in NG108–15 cells
    Morikawa, Morikawa; Fukuda, Fukuda; Mima, Mima; Shoda, Shoda; Kato, Kato; Mori, Mori
  • Metabotropic glutamate receptor‐mediated suppression of L‐type calcium current in acutely isolated neocortical neurons
    Sayer, Sayer; Schwindt, Schwindt; Crill, Crill
  • Neuropeptide Y receptors differentially modulate G‐protein‐activated inwardly rectifying K + channels and high‐voltage‐activated Ca 2+ channels in rat thalamic neurons
    Sun, Sun; Huguenard, Huguenard; Prince, Prince

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off