kn-62 and iberiotoxin

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been described as a biochemical switch that is turned on by increases in intracellular calcium to mediate synaptic plasticity. Here, we show that reductions in CaMKII activity trigger persistent increases in intrinsic excitability. In spontaneously firing vestibular nucleus neurons, CaMKII activity is near maximal, and blockade of CaMKII activity increases excitability by reducing BK-type calcium-activated potassium currents. Firing rate potentiation, a form of plasticity in which synaptic inhibition induces long-lasting increases in excitability, is occluded by prior blockade of CaMKII and blocked by addition of constitutively active CaMKII. Reductions in CaMKII activity are necessary and sufficient to induce firing rate potentiation and may contribute to motor learning in the vestibulo-ocular reflex.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Action Potentials; Animals; Animals, Newborn; Blotting, Western; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Enzyme Activation; Enzyme Inhibitors; Immunohistochemistry; In Vitro Techniques; Mice; Mice, Inbred C57BL; Neural Inhibition; Neurons; Patch-Clamp Techniques; Peptide Fragments; Peptides; Statistics, Nonparametric; Time Factors; Vestibular Nuclei