Biomedical subjects

R Huganir

Publications and source records attributed to R Huganir.

3 recordsLinked to original sources

PubMed2001

Activation of silent synapses by rapid activity-dependent synaptic recruitment of AMPA receptors.

Many recent studies have shown that excitatory synapses can contain NMDA receptor responses in the absence of functional AMPA receptors and are therefore postsynaptically silent at resting membrane potentials. The activation of silent synapses via the rapid acquisition of AMPA receptor responses may be important in synaptic plasticity and neuronal development. Our recent immunocytochemical studies that used cultured hippocampal neurons have provided evidence for "morphological silent synapses" that physically contain NMDA receptors but no AMPA receptors. Here we show that the activation of NMDA receptors by spontaneous synaptic activity results in the rapid recruitment of AMPA receptors into these morphological silent synapses within minutes. In parallel, we find a significant increase in the frequency of AMPA receptor-mediated miniature EPSCs (mEPSCs). NMDA receptor activation also results in a mobilization of calcium/calmodulin (CaM) kinase II to synapses and an increase in the phosphorylation of surface AMPA receptors on the major CaM kinase II phosphorylation site. These results demonstrate that AMPA receptors can be modified and recruited rapidly to silent synapses via the activation of NMDA receptors by spontaneous synaptic activity.

Action Potentials↗

PubMed1989

Cl- channels in CF: lack of activation by protein kinase C and cAMP-dependent protein kinase.

Secretory chloride channels can be activated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in normal airway epithelial cells but not in cells from individuals with cystic fibrosis (CF). In excised, inside-out patches of apical membrane of normal human airway cells and airway cells from three patients with CF, the chloride channels exhibited a characteristic outwardly rectifying current-voltage relation and depolarization-induced activation. Channels from normal tissues were activated by both cAMP-dependent protein kinase and protein kinase C. However, chloride channels from CF patients could not be activated by either kinase. Thus, gating of normal epithelial chloride channels is regulated by both cAMP-dependent protein kinase and protein kinase C, and regulation by both kinases is defective in CF.

Adult↗

PubMed1985

Protein phosphorylation and neuronal function.

Studies in the past several years have provided direct evidence that protein phosphorylation is involved in the regulation of neuronal function. Electrophysiological experiments have demonstrated that three distinct classes of protein kinases, i.e., cyclic AMP-dependent protein kinase, protein kinase C, and CaM kinase II, modulate physiological processes in neurons. Cyclic AMP-dependent protein kinase and kinase C have been shown to modify potassium and calcium channels, and CaM kinase II has been shown to enhance neurotransmitter release. A large number of substrates for these protein kinases have been found in neurons. In some cases (e.g., tyrosine hydroxylase, acetylcholine receptor, sodium channel) these proteins have a known function, whereas most of these proteins (e.g., synapsin I) had no known function when they were first identified as phosphoproteins. In the case of synapsin I, evidence now suggests that it regulates neurotransmitter release. These studies of synapsin I suggest that the characterization of previously unknown neuronal phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons.

Animals↗