Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells.

Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion... The mode of action of ACh antagonists on the parasympathetic neurones of the submandibular ganglion of the rat was studied by means of a two‐micro‐electrode voltage‐clamp technique. The currents produced by various agonists (carbachol, ACh, suberylcholine) were studied in steady state and after voltage steps, before and after perfusion of various antagonists. 2. For three antagonists (tubocurarine, hexamethonium, decamethonium) the blocking action increases with hyperpolarization. For three other antagonists (surugatoxin, trimetaphan, mecamylamine) the effects observed at low concentrations appear to be independent of membrane potential, although in some cases voltage dependence of the block was observed for mecamylamine. 3. The blocks the ‘open’ channel‐reception complex. The block produced by tubocurarine, hexamethonium and decamethonium increases with the agonist concentration, an observation which supports a ‘sequential’ scheme in which the antagonist blocks the ‘open’ channel‐receptor complex. The block produced by trimetaphan and mecamylamine decreases slightly with increased agonist concentration, which in turn suggests that these two compounds are competitive antagonists, preventing binding of the agonists to the closed channel‐receptor complex. 4. In the cases where the block is voltage dependent, voltage jumps trigger slow relaxations which are not present in control conditions. In the case of tubocurarine and hexamethonium, the relaxation following a hyperpolarizing voltage jump corresponds to a decrease in conductance. In the case of decamethonium, the slow relaxation is in the opposite direction. 5. The slow relaxations observed with tubocurarine and hexamethonium are speeded by an increase of the antagonist concentration; the slow relaxations observed with decamethonium are slowed by an increase of the decamethonium concentration. 6. The steady‐state observations and the relaxations can be interpreted in terms of a scheme in which tubocurarine, hexamethonium and decamethonium act mainly by blocking the channels opened by the cholinergic agonists. 7. The two types of slow relaxation are those predicted if tubocurarine and hexamethonium dissociate slowly from the channel, and decamethonium rapidly. 8. An additional effect of tubocurarine is described, which consists of a potentiation of the rising phase of the response to an ionophoretic pulse. Possible mechanisms of this effect are discussed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Physiology Wiley

Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells.

The Journal of Physiology, Volume 295 (1) – Oct 1, 1979

Loading next page...
 
/lp/wiley/studies-on-the-mechanism-of-action-of-acetylcholine-antagonists-on-rat-vf0g0Yenes
Publisher
Wiley
Copyright
© 2014 The Physiological Society
ISSN
0022-3751
eISSN
1469-7793
D.O.I.
10.1113/jphysiol.1979.sp012958
Publisher site
See Article on Publisher Site

Abstract

The mode of action of ACh antagonists on the parasympathetic neurones of the submandibular ganglion of the rat was studied by means of a two‐micro‐electrode voltage‐clamp technique. The currents produced by various agonists (carbachol, ACh, suberylcholine) were studied in steady state and after voltage steps, before and after perfusion of various antagonists. 2. For three antagonists (tubocurarine, hexamethonium, decamethonium) the blocking action increases with hyperpolarization. For three other antagonists (surugatoxin, trimetaphan, mecamylamine) the effects observed at low concentrations appear to be independent of membrane potential, although in some cases voltage dependence of the block was observed for mecamylamine. 3. The blocks the ‘open’ channel‐reception complex. The block produced by tubocurarine, hexamethonium and decamethonium increases with the agonist concentration, an observation which supports a ‘sequential’ scheme in which the antagonist blocks the ‘open’ channel‐receptor complex. The block produced by trimetaphan and mecamylamine decreases slightly with increased agonist concentration, which in turn suggests that these two compounds are competitive antagonists, preventing binding of the agonists to the closed channel‐receptor complex. 4. In the cases where the block is voltage dependent, voltage jumps trigger slow relaxations which are not present in control conditions. In the case of tubocurarine and hexamethonium, the relaxation following a hyperpolarizing voltage jump corresponds to a decrease in conductance. In the case of decamethonium, the slow relaxation is in the opposite direction. 5. The slow relaxations observed with tubocurarine and hexamethonium are speeded by an increase of the antagonist concentration; the slow relaxations observed with decamethonium are slowed by an increase of the decamethonium concentration. 6. The steady‐state observations and the relaxations can be interpreted in terms of a scheme in which tubocurarine, hexamethonium and decamethonium act mainly by blocking the channels opened by the cholinergic agonists. 7. The two types of slow relaxation are those predicted if tubocurarine and hexamethonium dissociate slowly from the channel, and decamethonium rapidly. 8. An additional effect of tubocurarine is described, which consists of a potentiation of the rising phase of the response to an ionophoretic pulse. Possible mechanisms of this effect are discussed.

Journal

The Journal of PhysiologyWiley

Published: Oct 1, 1979

There are no references for this article.

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