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Threshold effects of N-methyl D-aspartate (NMDA) and 2-amino 5-phosphono valeric acid (2APV) on the spontaneous activity of neocortical single neurones in the urethane anaesthetised rat.

Spontaneous activity of single neurones in neocortex was sampled using pairs of microelectrodes in rats anaesthetised with urethane. In confirmation of previous studies, many cells recorded from middle layers characteristically fired in bursts, the onset times of which were synchronous both unilaterally and bilaterally. Iontophoresis of 2APV onto such cells either caused an abolition of bursts or a reduction in spikes per burst. In the latter case action potentials which occurred later in the burst were preferentially abolished. Iontophoresis of NMDA onto the same cells caused a prolongation of bursts with minimal effect on intraburst interspike interval. In interactive trials with the two drugs the effect of NMDA could be abolished by 2APV, and NMDA counteracted the effect of 2APV. It is concluded that spontaneous burst generation in neocortex during urethane anaesthesia is generated through a cortical NMDA/2APV-sensitive receptor mechanism.

Action Potentials↗

Influence of chain ordering on the selectivity of dipalmitoylphosphatidylcholine bilayer membranes for permeant size and shape.

The effects of lipid chain packing and permeant size and shape on permeability across lipid bilayers have been investigated in gel and liquid crystalline dipalmitoylphosphatidylcholine (DPPC) bilayers by a combined NMR line-broadening/dynamic light scattering method using seven short-chain monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, and trimethylacetic acid) as permeants. The experimental permeability coefficients are compared with the predictions of a bulk solubility diffusion model in which the bilayer membrane is represented as a slab of bulk hexadecane. Deviations of the observed permeability coefficients (Pm) from the values predicted from solubility diffusion theory (Po) lead to the determination of a correction factor, the permeability decrement f (= Pm/Po), to account for the effects of chain ordering. The natural logarithm of f has been found to correlate linearly with the inverse of the bilayer free surface area with slopes of 25 +/- 2, 36 +/- 3, 45 +/- 8, 32 +/- 12, 33 +/- 4, 49 +/- 12, and 75 +/- 6 A2 for formic acid, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, and trimethylacetic acid, respectively. The slope, which measures the sensitivity of the permeability coefficient of a given permeant to bilayer chain packing, exhibits an excellent linear correlation (r = 0.94) with the minimum cross-sectional area of the permeant and a poor correlation (r = 0.59) with molecular volume, suggesting that in the bilayer interior the permeants prefer to move with their long principal axis along the bilayer normal. Based on these studies, a permeability model combining the effects of bilayer chain packing and permeant size and shape on permeability across lipid membranes is developed.

1,2-Dipalmitoylphosphatidylcholine↗