1293276

umls-concept:C0014898, umls-concept:C0027882, umls-concept:C0032821, umls-concept:C0205374, umls-concept:C0205396, umls-concept:C0521116, umls-concept:C0553251, umls-concept:C1280500, umls-concept:C1611588

1. A two-microelectrode voltage clamp was used to determine the effects of n-butanol, n-hexanol, n-octanol, n-decanol and methyl hexanoate on a transient potassium (IA) current in identified Helix aspersa neurones. Experiments were carried out at a temperature of 10-12 degrees C. 2. Each n-alkanol reversibly reduced the amplitude of the IA current. Logarithmic dose-response curves for the current reduction by each homologue were sigmoidal and had slope factors of around four. The concentrations required to reduce the peak (with time) current at -30 mV by 50% (ED50 +/- fitted standard error) were: 57 +/- 5 mM (n-butanol); 2.0 +/- 0.1 mM (n-hexanol); 0.28 +/- 0.02 mM (n-octanol) and 0.016 +/- 0.001 mM (n-decanol). Methyl hexanoate also reduced the current amplitude, with an ED50 of 1-2 mM. The Helix IA current thus showed a similar sensitivity to n-alkanols to that of squid and rat sodium currents but was rather more sensitive than the squid delayed rectifier potassium current. 3. The n-alkanol ED50 concentrations were used to calculate a standard free energy per methylene group for adsorption to a site of action in the cell of -3.1 +/- 0.2 kJ/mol. This suggested a hydrophobic site or sites of action. The regularity of the change in free energy with chain length was maintained up to, and including, n-decanol. This implied that the site(s) could accommodate a ten-carbon chain as readily as an eight-carbon chain. 4. The voltage dependencies of IA current activation and steady-state inactivation were not consistently altered by treatment with n-alkanols at concentrations around or above their current suppression ED50 concentrations. 5. The kinetics of current activation and inactivation were affected, particularly by lower chain length compounds. At 60 mM n-butanol reduced the time constant for development of inactivation of open channels (tau b) by 56%, while 0.016 mM n-decanol produced only a 13% reduction. n-Butanol (60 mM) also caused a substantial (76%) reduction in the time constant for development of inactivation in channels which were presumed to be closed. The effects of n-alkanols on the current time-to-peak (tc) were complex, showing both increases and decreases, but these actions also declined with chain length. Methyl hexanoate (1 mM) reduced tau b by around 30% and tc by around 20%. 6. n-Alkanols have now been shown to inhibit a number of voltage-gated ion conductances.(ABSTRACT TRUNCATED AT 400 WORDS)

http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-14225257, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-1647732, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-1846229, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-1849060, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-1881453, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-1908562, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2010814, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2122519, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2122520, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2171374, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-233577, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-234036, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2415915, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2425895, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2443693, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2444677, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2447587, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2541793, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2561786, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2848131, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-2914145, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-3194020, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-3349082, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-3395541, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-3746676, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-3790564, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-3828333, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-4519599, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-465879, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-5564761, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-5575340, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-591912, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-6257298, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-6312030, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-723953, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-7264970, http://linkedlifedata.com/resource/pubmed/commentcorrection/1293276-850203

http://linkedlifedata.com/resource/pubmed/journal/0266262

http://linkedlifedata.com/resource/pubmed/chemical/Alcohols, http://linkedlifedata.com/resource/pubmed/chemical/Hexanoic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, http://linkedlifedata.com/resource/pubmed/chemical/methyl caproate

Oct

pubmed-author:ElliottJ RJR, pubmed-author:HarperA AAA, pubmed-author:WinpennyJ PJP

456

Y

2010-9-7

1992

Department of Anatomy and Physiology, The University, Dundee.