Characteristics of drug concentration profiles for picoejection studies of brainstem neurons

The picoejection technique has been used to study the roles of various neurotransmitter receptors in the generation/control of respiratory neuronal discharge patterns. This method has the ability to produce quasi‐steady‐state dose‐dependent effects on neuronal discharge frequency patterns. While the drug barrel concentration (C o ) is known and ejection volume‐rates can be measured, the drug concentration as a function of time and radial distance C(t,r) from the micropipette tip is not known. Accordingly, a mathematical compartmental model was developed and simulated, which allows the concentration profiles to be estimated for various diffusion rates and picoejection parameters. The model is based on Fick’s law (flux=‐D.dC/dr, where D is the diffusion coefficient) and spherical geometry. Each of the 1020 compartments represents the volume of a 1‐μm thick spherical shell centered at the tip of the pipette with the volume and surface area increasing with radial distance. The model gives C(t,r) in 1‐μm increments for 0 < r < 1020 μm. Simulation shows that C(t,r) can reach ~90% of max. in 2 min for r<150 μm and peak C(t,r) is ~linearly related to ejection pulse rate and spritz volume over a wide C(t,r) range. The model allows picoejection strategies to be optimized. Support: VA Merit 9952 and NIH GM059234.