ABSTRACT

Here Q represents the charge passed at the surface of the electrode, n is the number of electrons transferred per analyte molecule (two for catecholamines), and F is the Faraday constant (96,485 C/mol). The charge, Q, is obtained by integration of the current with respect to time of a current vs. time trace, such as the one shown in Figure 2C. Equation (4) has been used to obtain a quantitative distribution of transmitter concentration in a population of vesicles, as shown in Figure 12. The mean vesicular dopamine concentration calculated using this model is 148±7 mM. Previous estimates of concentration have been made using a known average vesicle radius (i.e., by electron microscopy) and an average vesicle amount (by amperometry). Using this method, a value of 99 mM has been reported by Finnegan et al. [12], which is in close agreement to the average value reported here. However, Finnegan et al. assumed a constant concentration of transmitter in the vesicles for their calculations. The model presented here sug-

This vesicular catecholamine concentration distribution has important ramifications to neurotransmission. Although the mean concentration reported in this study is 148 mM, it is clear from the histogram in Figure 12 that the most likely release event (mode) contains catecholamine at a concentration three times smaller than the mean. This fact becomes important if a small number of vesicles are released per stimulus. If hundreds of vesicles are released, the total amount of messenger released will follow the distribution shown. However, if only a few vesicles undergo release, the most likely release event will contain neurotransmitter at a much smaller concentration and, therefore, may not have as great an effect on the postsynaptic cell or, perhaps more important, on the outlying cells surrounding the synapse. Again, this is particularly important when one considers that the neurotransmitter-receptor interaction is an equilibrium-based reaction that could be highly dependent on transmitter concentration if the receptors are not saturated.