The effects of short-chain phospholipids on the acetylcholine-activated ion channel.
The effects of a homologous series of short-chain phospholipids, the phosphatidylcholines from dihexanoylglycerophosphocholine (Hxo2GroPCho) to didecanoylglycerophosphocholine, on the nicotinic acetylcholine-activated ion channel in cultured rat muscle cells were investigated. Standard patch-clamp techniques were used to measure single-channel currents in excised patches. All phospholipids investigated markedly reduced the frequency of channel opening in a concentration-dependent manner. Other parameters, such as the mean open time, the duration and frequency of brief closures within an opening, and channel amplitude, were not significantly affected. This effect was independent of the side of the membrane to which the phospholipid was added. Dose/response curves were obtained for Hxo2-, diheptanoyl(Hpo2)- and dinonanoyl(Nno2)GroPCho. The concentration leading to 50% reduction in channel activity decreased upon ascending the homologous series from 16.69 microM Hxo2GroPCho to 4.52 microM and 0.043 microM for Hpo2- and Nno2GroPCho, respectively. The more hydrophobic the molecule the more effective it was, and hence the higher its affinity to the binding site. Calculation of the standard free-energy change of adsorption into the site led to a value of -3.1 kJ/mol, which indicates a very hydrophobic binding site. In conclusion, the phospholipids interact in a non-specific way with the lipid membrane thereby disturbing proper channel function.
Braun
M S
MS
Physiological Laboratory, University of Cambridge, UK.
Haydon
D A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*
D000779:Anesthetics, Local; D010713:Phosphatidylcholines; D011950:Receptors, Cholinergic; C032166:1,2-hexanoylphosphatidylcholine; D000109:Acetylcholine