Pore formation by 6-ketocholestanol in phospholipid monolayers and its interpretation by a general nucleation-and-growth model accounting for the sigmoidal shape of voltage-clamp curves of ion channels.
6-Ketocholestanol (KC), a steroid that differs from cholesterol mainly by the presence of a carbonyl group, forms pores inside a dioleoylphosphatidylcholine monolayer self-assembled on mercury by a mechanism similar to that of channel-forming peptides and proteins. The potential steps responsible for pore formation by KC molecules give rise to potentiostatic charge vs time curves whose sigmoidal shape and potential dependence can be quantitatively interpreted on the basis of a mechanism of nucleation and growth of KC clusters. Pore formation by KC allows the penetration of thallous ions across the otherwise impermeable phosphatidylcholine monolayer, while pore disruption taking place at more negative potentials causes a drop in thallous ion permeation. Pore disruption is also accounted for by a mechanism of nucleation and growth of holes inside the KC clusters. The kinetic model of nucleation and growth is general, and accounts quantitatively for the sigmoidal shape and potential dependence of the classical Hodgkin-Huxley voltage-clamp curves of potassium channels in squid giant axon,(1) using a minimum number of free parameters.
Becucci
Lucia
L
Department of Chemistry, Florence University, Sesto Fiorentino (Florence) 50019, Italy.
Moncelli
Maria Rosa
MR
Guidelli
Rolando
R
D000818:Animals; D001369:Axons / Q000378:metabolism; D049832:Decapodiformes; D004553:Electric Conductivity; D057927:Hydrophobic and Hydrophilic Interactions; D007473:Ion Channels / Q000737:chemistry*; D007653:Ketocholesterols / Q000737:chemistry*; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D010713:Phosphatidylcholines / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity
D007473:Ion Channels; D007653:Ketocholesterols; D010713:Phosphatidylcholines; D015221:Potassium Channels; C063833:6-ketocholestanol; C017251:1,2-oleoylphosphatidylcholine