One class of cells had an initial standing signal indicative of high extracellular H+ adjacent to
the cell membrane; challenge with glutamate, kainate or high extracellular potassium induced an extracellular alkalinization. This alkalinization was reduced by the calcium channel blockers nifedipine and cobalt. A second class of cells displayed Selleckchem Pexidartinib spontaneous oscillations in extracellular H+ that were abolished by cobalt, nifedipine and low extracellular calcium. A strong correlation between changes in intracellular calcium and extracellular proton flux was detected in experiments simultaneously monitoring intracellular calcium and extracellular H+. A third set of cells was characterized by a standing extracellular alkalinization which was turned into an acidic signal by cobalt. In this last set of cells, addition of glutamate or high extracellular potassium did not significantly alter the proton signal. Taken together, the response characteristics of all three sets of neurons are most parsimoniously explained by activation of a plasma membrane Ca2+ ATPase pump, with an extracellular alkalinization resulting from exchange of intracellular calcium for extracellular H+. These findings argue strongly against the hypothesis that H+ release from horizontal cells Proteasome inhibitor mediates lateral
inhibition in the outer retina. “
“Tricyclic antidepressants (TCAs) have been used to treat melancholic depression, which has been associated
with elevated hypothalamic–pituitary–adrenocortical (HPA) axis activity, whereas patients suffering from atypical depression, which is often associated with decreased HPA axis activity, show preferential responsiveness to monoamine oxidase inhibitors (MAOIs). We previously reported drug-specific effects of the TCA imipramine and the MAOI phenelzine also on HPA axis-relevant endpoints in mice that may explain differential antidepressant responses in melancholic vs. atypical depression. However, selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in both melancholic and atypical depression. We therefore hypothesized that SSRIs would share HPA axis-related effects with either TCAs or MAOIs. To test this hypothesis, we measured HPA axis-relevant gene expression in male C57BL/6 mice treated for 5 weeks with 10 mg/kg/day fluoxetine. To control for potential fluoxetine-induced changes in glucocorticoid secretion, mice were adrenalectomized and given fixed levels of glucocorticoids. Fluoxetine decreased glucocorticoid receptor (GR) gene expression in the prefrontal cortex, amygdala, locus coeruleus and dorsal raphé nucleus, and increased locus coeruleus tyrosine hydroxylase and dorsal raphé nucleus tryptophan hydroxylase-2 (TPH2) gene expression.