Alpha-subunit of calcium/calmodulin-dependent protein kinase II enhances gamma-aminobutyric acid and inhibitory synaptic responses of rat neurons in vitro

1. Here we report that in acutely isolated rat spinal dorsal horn neurons, the gamma-aminobutyric acid-A (GABAA) receptor can be regulated by calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced GABAA-receptor-activated current recorded with the use of the whole cell patch-clamp technique. This effect was associated with reduced desensitization of GABA responses. 2. GABA-induced currents are also potentiated by calyculin A, an inhibitor of protein phosphatases 1 and 2A. 3. Conventional intracellular recordings were made from hippocampal CA1 neurons in slices to determine the effect of intracellular application of CaM-KII on inhibitory synaptic potentials evoked by electrical stimulation of the stratum oriens/alveus. The inhibitory synaptic potential was enhanced by CaM-KII; this mechanism may contribute to long-term enhancement of inhibitory synaptic transmission and may also play a role in other forms of plasticity in the mammalian brain.

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Alpha subunit of calcium/calmodulin-dependent protein kinase enhances excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons

Journal of Neurophysiology ◽

10.1152/jn.1994.72.5.2525 ◽

1994 ◽

Vol 72 (5) ◽

pp. 2525-2531 ◽

Cited By ~ 45

Author(s):

M. Kolaj ◽

R. Cerne ◽

G. Cheng ◽

D. A. Brickey ◽

M. Randic

Keyword(s):

Protein Kinase ◽

Synaptic Transmission ◽

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Alpha Subunit ◽

Patch Clamp Technique ◽

Dependent Protein Kinase ◽

Spinal Dorsal ◽

Calcium Calmodulin Dependent ◽

Dependent Protein

1. Here we report that in acutely isolated rat spinal dorsal horn (DH) neurons, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) receptors can be regulated by endogenous and exogenous calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced AMPA/kainate and NMDA currents recorded with the use of the whole cell patch-clamp technique. 2. Microcystin, a nonselective phosphatases inhibitor, also enhances AMPA and NMDA responses. 3. Conventional intracellular recordings were made from substantia gelatinosa neurons in spinal cord slices to determine the effect of intracellular application of CaM-KII on excitatory synaptic potentials evoked by electrical stimulation of primary afferent fibers. Excitatory synaptic transmission was enhanced by CaM-KII, which is consistent with the importance of phosphorylation of the postsynaptic AMPA/kainate and NMDA receptor-ion complexes in the short- and long-term changes in synaptic transmission.

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Localization of alpha type II calcium calmodulin-dependent protein kinase at glutamatergic but not gamma-aminobutyric acid (GABAergic) synapses in thalamus and cerebral cortex.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.93.14.7332 ◽

1996 ◽

Vol 93 (14) ◽

pp. 7332-7336 ◽

Cited By ~ 116

Author(s):

X. B. Liu ◽

E. G. Jones

Keyword(s):

Cerebral Cortex ◽

Protein Kinase ◽

Aminobutyric Acid ◽

Type Ii ◽

Gamma Aminobutyric Acid ◽

Dependent Protein Kinase ◽

Calcium Calmodulin Dependent ◽

Gabaergic Synapses ◽

Dependent Protein ◽

Alpha Type

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Functional identification of the promoter for the gene encoding the alpha subunit of calcium/calmodulin-dependent protein kinase II.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.92.5.1659 ◽

1995 ◽

Vol 92 (5) ◽

pp. 1659-1663 ◽

Cited By ~ 16

Author(s):

N. J. Olson ◽

T. Masse ◽

T. Suzuki ◽

J. Chen ◽

D. Alam ◽

...

Keyword(s):

Protein Kinase ◽

Alpha Subunit ◽

Functional Identification ◽

Dependent Protein Kinase ◽

Gene Encoding ◽

Calcium Calmodulin Dependent ◽

Protein Kinase Ii ◽

Dependent Protein

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Ischemia-Induced Neuronal Damage: A Role for Calcium/Calmodulin-Dependent Protein Kinase II

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199601000-00001 ◽

1996 ◽

Vol 16 (1) ◽

pp. 1-6 ◽

Cited By ~ 74

Author(s):

M. Neal Waxham ◽

James C. Grotta ◽

Alcino J. Silva ◽

Roger Strong ◽

Jaroslaw Aronowski

Keyword(s):

Protein Kinase ◽

Neuronal Damage ◽

Alpha Subunit ◽

Cam Kinase ◽

Wild Type ◽

Dependent Protein Kinase ◽

Knock Out ◽

Calcium Calmodulin Dependent ◽

Protein Kinase Ii ◽

Dependent Protein

Calcium/calmodulin-dependent protein kinase II (CaM-kinase) is a central enzyme in regulating neuronal processes. Imbalances in the activity and distribution of this enzyme have been reported following in vivo ischemia, and sustained decreases in activity correlate with subsequent neuronal death. In this report, mice that had been rendered deficient in the alpha subunit of CaM-kinase using gene knock-out technology were utilized to determine whether this enzyme is causally related to ischemic damage. Using a focal model of cerebral ischemia, we showed that homozygous knock-out mice lacking the alpha subunit exhibited an infarct volume almost twice that of wild-type litter mates. Heterozygous mice exhibited slightly less damage following ischemia than did homozygous mice, but infarct volumes remained significantly larger than those of wild-type litter mates. We conclude that reduced amounts of the alpha subunit of CaM-kinase predisposes neurons to increased damage following ischemia and that any perturbation that decreases the amount or activity of the enzyme will produce enhanced susceptibility to neuronal damage.

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