Abstract
Ca(2+)-dependent mechanisms are important in regulating synaptic transmission. The results herein indicate that whole-cell perfusion of inositol 1,4,5-trisphosphate receptor (IP(3)R) agonists greatly enhanced excitatory postsynaptic current (EPSC) amplitudes in postsynaptic hippocampal CA1 neurons. IP(3)R agonist-mediated increases in synaptic transmission changed during development and paralleled age-dependent increases in hippocampal type-1 IP(3)Rs. IP(3)R agonist-mediated increases in EPSC amplitudes were inhibited by postsynaptic perfusion of inhibitors of Ca(2+)/calmodulin, PKC and Ca(2+)/calmodulin-dependent protein kinase II. Postsynaptic perfusion of inhibitors of smooth endoplasmic reticulum (SER) Ca(2+)-ATPases, which deplete intracellular Ca(2+) stores, also enhanced EPSC amplitudes. Postsynaptic perfusion of the IP(3)R agonist adenophostin (AdA) during subthreshold stimulation appeared to convert silent to active synapses; synaptic transmission at these active synapses was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Postsynaptic IP(3)R-mediated Ca(2+) release also produced a significant increase in spontaneous EPSC frequency. These results indicate that Ca(2+) release from intracellular stores play a key role in regulating the function of postsynaptic AMPARs.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
2-Amino-5-phosphonovalerate / pharmacology
-
6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
-
Adenosine / analogs & derivatives*
-
Adenosine / pharmacology
-
Age Factors
-
Animals
-
Animals, Newborn
-
Bicuculline / pharmacology
-
Blotting, Western / methods
-
Calcium / metabolism*
-
Calcium Channel Agonists / pharmacology
-
Calcium Channels / physiology*
-
Drug Interactions
-
Electric Stimulation / methods
-
Enzyme Inhibitors / pharmacology
-
Excitatory Amino Acid Antagonists / pharmacology
-
Excitatory Postsynaptic Potentials / drug effects
-
Excitatory Postsynaptic Potentials / physiology
-
Excitatory Postsynaptic Potentials / radiation effects
-
GABA Antagonists / pharmacology
-
Gene Expression Regulation, Developmental / drug effects
-
Gene Expression Regulation, Developmental / physiology*
-
Hippocampus / cytology*
-
Hippocampus / growth & development
-
In Vitro Techniques
-
Indoles / pharmacology
-
Inositol 1,4,5-Trisphosphate / analogs & derivatives*
-
Inositol 1,4,5-Trisphosphate / pharmacology
-
Inositol 1,4,5-Trisphosphate Receptors
-
Neurons / drug effects
-
Neurons / physiology*
-
Neurons / radiation effects
-
Patch-Clamp Techniques / methods
-
Picrotoxin / pharmacology
-
Rats
-
Receptors, Cytoplasmic and Nuclear / agonists
-
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
-
Receptors, Cytoplasmic and Nuclear / physiology*
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / physiology*
-
Thapsigargin / pharmacology
-
Time Factors
Substances
-
Calcium Channel Agonists
-
Calcium Channels
-
Enzyme Inhibitors
-
Excitatory Amino Acid Antagonists
-
GABA Antagonists
-
Indoles
-
Inositol 1,4,5-Trisphosphate Receptors
-
Receptors, Cytoplasmic and Nuclear
-
Picrotoxin
-
3-deoxy-3-fluoroinositol 1,4,5-trisphosphate
-
adenophostin A
-
Thapsigargin
-
6-Cyano-7-nitroquinoxaline-2,3-dione
-
2-Amino-5-phosphonovalerate
-
Inositol 1,4,5-Trisphosphate
-
Adenosine
-
Calcium
-
cyclopiazonic acid
-
Bicuculline