AMPA-type glutamate receptors mediate most excitatory postsynaptic currents (EPSCs) at central synapses, and their conductance determines in part the size of EPSCs. The conductance of a recombinant AMPA receptor depends on the number of agonist molecules bound to the channel. Here we tested whether native AMPA and kainate receptors show this behavior in outside-out patches from neurons in situ by measuring conductance levels of single channels over a wide range of agonist concentrations. We found that the conductance of AMPA, but not kainate, receptors depended strongly on agonist concentration. Our results suggest that alterations in the glutamate concentration in the synaptic cleft may change the apparent unitary conductance of postsynaptic AMPA receptors.
The GABA (gamma-aminobutyric-acid)-containing periglomerular (PG) cells provide the first level of inhibition to mitral and tufted (M/T) cells, the output neurons of the olfactory bulb. We find that stimulation of PG cells of the rat olfactory bulb results in self-inhibition: release of GABA from an individual PG cell activates GABA(A) receptors on the same neuron. PG cells normally contain high concentrations of intracellular chloride and consequently are depolarized by GABA. Despite this, GABA inhibits PG cell firing by shunting excitatory signals. Finally, GABA released during self-inhibition may spill over to neighboring PG cells, resulting in a lateral spread of inhibition. Given the gatekeeping role of PG cells in the olfactory network, GABA-mediated self-inhibition will favor M/T cell excitation during intense sensory stimulation.
The insulin receptor is a tyrosine kinase receptor that is found in mammalian brain and at high concentrations in the bag cell neurons of Aplysia. We show here that insulin causes an acute rise in intracellular Ca2+ concentration ([Ca2+]i) in these neurons and triggers release of neuropeptide. The insulin-sensitive intracellular Ca2+ pool differs pharmacologically from previously described Ca2+ stores that are sensitive to inositol trisphosphate and from mitochondrial Ca2+ stores. Insulin, but not thapsigargin, stimulates Ca2+ release at the distal tips of neurites, the presumed site of neuropeptide secretion. The effects of insulin on intracellular Ca2+ release and neuropeptide secretion occur without triggering spontaneous action potentials. The insulin-sensitive rise in [Ca2+]i moves into the distal tips of neurites after exposure to a cyclic AMP analogue, a treatment that causes a similar translocation of neuronal vesicles. Our data indicate that Ca2+ release from a distinct intracellular pool associated with secretory vesicles may contribute to secretion of neuropeptide in the absence of neuronal discharge.
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