Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release.
In several neuronal preparations, the ryanodine-sensitive calcium store was reported to participate in the generation of slow afterhyperpolarization currents (IsAHP) involved in spike frequency adaptation. We show that calcium release from the ryanodine-sensitive calcium store is a major determinant of the triggering of IsAHP in mouse CA1 pyramidal neurons. Whole-cell patch clamp recordings in hippocampus slices show that the intracellular calcium stores depletion using an inhibitor of the endoplasmic reticulum Ca2+-ATPase (5 microM cyclopiazonic acid), as well as the specific blockade of ryanodine receptors (100 microM ryanodine) both reduced the IsAHP by about 70%. Immunohistology, using an anti-RyR3 specific antibody, indicates that RyR3 expression is particularly enriched in the CA1 apical dendrites (considered as the most important site for sAHP generation). We show that our anti-RyR3 antibody acts as a functional RyR3 antagonist and induced a reduction in IsAHP by about 70%. The additional ryanodine application (100 micro M) did not further affect IsAHP, thus excluding RyR2 in IsAHP activation. Our results argue in favor of a specialized function of RyR3 in CA1 pyramidal cells in triggering IsAHP due to their localization in the apical dendrite.
van de Vrede
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Y
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France.
Fossier
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P
Baux
G
G
Joels
M
M
Chameau
P
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
D000906:Antibodies; D015220:Calcium Channels; D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium