Predictions of the EC50 for Action Potential Block for Aliphatic Solutes

Predictions of the EC50 for Action Potential Block for Aliphatic Solutes Experiments were conducted to test the hypothesis that aliphatic hydrocarbons bind to pockets/crevices of sodium (Na+) channels to cause action potential (AP) block. Aliphatic solutes exhibiting successively greater octanol/water partitition coefficients (K ow) were studied. Each solute blocked Na+ channels. The 50% effective concentration (EC50) to block APs could be mathematically predicted as a function of the solute’s properties. The solutes studied were methyl ethyl ketone (MEK), cyclohexanone, dichloromethane, chloroform and triethylamine (TriEA); the K ow increased from MEK to TriEA. APs were recorded from frog nerves, and test solutes were added to Ringer’s solution bathing the nerve. When combined with EC50s for solutes with log K ows < 0.29 obtained previously, the solute EC50s could be predicted as a function of the fractional molar volume (dV/dm = [dV/dn]/100), polarity (P) and the hydrogen bond acceptor basicity (β) by the following equation: $$ {\text{EC}}_{{50}} = 2.612{\left( {10^{{{\left\{ { - 2.117{\left[ {{\text{dv}}/{\text{dm}}} \right]} + 0.6424{\text{P}} + 2.628\beta } \right\}}}} } \right)} $$ Fluidity changes cannot explain the EC50s. Each of the solutes blocks Na+ channels with little or no change in kinetics. Na+ channel block explains much of the EC50 data. EC50s are produced by a combination of effects including ion channel block, fluidity changes and osmotically induced structural changes. As the solute log K ow increases to values near 1 or greater, Na+ channel block dominates in determining the EC50. The results are consistent with the hypothesis that the solutes bind to channel crevices to cause Na+ channel and AP block. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Predictions of the EC50 for Action Potential Block for Aliphatic Solutes

Loading next page...
 
/lp/springer_journal/predictions-of-the-ec50-for-action-potential-block-for-aliphatic-EF0tW0UTi0
Publisher
Springer-Verlag
Copyright
Copyright © 2007 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-007-9087-z
Publisher site
See Article on Publisher Site

Abstract

Experiments were conducted to test the hypothesis that aliphatic hydrocarbons bind to pockets/crevices of sodium (Na+) channels to cause action potential (AP) block. Aliphatic solutes exhibiting successively greater octanol/water partitition coefficients (K ow) were studied. Each solute blocked Na+ channels. The 50% effective concentration (EC50) to block APs could be mathematically predicted as a function of the solute’s properties. The solutes studied were methyl ethyl ketone (MEK), cyclohexanone, dichloromethane, chloroform and triethylamine (TriEA); the K ow increased from MEK to TriEA. APs were recorded from frog nerves, and test solutes were added to Ringer’s solution bathing the nerve. When combined with EC50s for solutes with log K ows < 0.29 obtained previously, the solute EC50s could be predicted as a function of the fractional molar volume (dV/dm = [dV/dn]/100), polarity (P) and the hydrogen bond acceptor basicity (β) by the following equation: $$ {\text{EC}}_{{50}} = 2.612{\left( {10^{{{\left\{ { - 2.117{\left[ {{\text{dv}}/{\text{dm}}} \right]} + 0.6424{\text{P}} + 2.628\beta } \right\}}}} } \right)} $$ Fluidity changes cannot explain the EC50s. Each of the solutes blocks Na+ channels with little or no change in kinetics. Na+ channel block explains much of the EC50 data. EC50s are produced by a combination of effects including ion channel block, fluidity changes and osmotically induced structural changes. As the solute log K ow increases to values near 1 or greater, Na+ channel block dominates in determining the EC50. The results are consistent with the hypothesis that the solutes bind to channel crevices to cause Na+ channel and AP block.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jan 16, 2008

References

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 lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off