Modulatory interactions between norepinephrine and taurine, beta-alanine, gamma-aminobutyric acid and muscimol, applied iontophoretically to cerebellar purkinje cells

Abstract

Norepinephrine (NE) released iontophoretically or synaptically onto cerebellar Purkinje cells has been shown to have an overall effect of enhancing GABA-mediated inhibition. This study was undertaken to characterize further the observed NE facilitating action by comparing the interaction of iontophoretically applied NE with depressions in Purkinje cell activity induced by direct application of the putative amino acid neurotransmitters, taurine, β-alanine and γ-aminobutyric acid (GABA). Norepinephrine exerted differential effects on the actions of the amino acids, consistently augmenting GABA-induced inhibition while having minimal and inconsistent effects on inhibitions induced by taurine and β-alanine. However, Purkinje cell inhibitory responses produced by iontophoresis of muscimol, an agent which binds to GABA receptors but is not an effective substrate for the GABA uptake system, were routinely enhanced by NE application. In comparison, continuous application of GABA at low iontophoretic currents showed no ability to augment inhibitions in Purkinje cell firing induced by superimposed GABA pulses. These results argue for a mode of facilitation of Purkinje cell inhibitions by NE that is selective for GABA vs other inhibitory amino acid agents. Moreover, this facilitation is likely to be a postsynaptic phenomenon since it appears independent of presynaptic transmitter release and of the GABA uptake system.