The absence of a major Ca2+ signaling pathway in GABAergic neurons of the hippocampus.
The Ca2+/calmodulin-dependent protein phosphatase 2B or calcineurin (CN) participates in several Ca2+-dependent signal transduction cascades and, thus, contributes to the short and long term regulation of neuronal excitability. By using a specific antibody to CN, we demonstrate its absence from hippocampal interneurons and illustrate a physiological consequence of such CN deficiency. Consistent with the lack of CN in interneurons as detected by immunocytochemistry, the CN inhibitors FK-506 or okadaic acid significantly prolonged N-methyl-D-aspartate channel openings recorded in the cell-attached mode in hippocampal principal cells but not those recorded in interneurons. Interneurons were also devoid of Ca2+/calmodulin-dependent protein kinase IIalpha, yet many of their nuclei contained the cyclic AMP-responsive element binding protein. On the basis of the CN and Ca2+/calmodulin-dependent protein kinase IIalpha deficiency of interneurons, entirely different biochemical mechanisms are expected to govern Ca2+-dependent neuronal plasticity in interneurons versus principal cells.
Sík
A
A
Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony utca 43, Budapest, H-1083, Hungary.
Hájos
N
N
Gulácsi
A
A
Mody
I
I
Freund
T F
TF
D000818:Animals; D019703:Calcineurin / Q000172:deficiency; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000172:deficiency; D002147:Calmodulin / Q000172:deficiency; D002451:Cell Compartmentation; D017362:Cyclic AMP Response Element-Binding Protein / Q000302:isolation & purification; D004594:Electrophysiology / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002147:Calmodulin; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517675:Camk2a protein, rat; D019703:Calcineurin; D002118:Calcium