Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor

Numerous studies using peptide inhibitors have confirmed the block of LTP.

“Numerous studies using peptide inhibitors have confirmed the block of LTP (200–203).”

Pharmacological inhibition of CaMKII activity has generally been reported not to affect synaptic responses.

“In addition, pharmacological inhibition of CaMKII activity has generally been reported not to affect synaptic responses (198, 200–203, 357, 358).”

The slow time course of inhibition is not due to slow access of the inhibitors to the site of action, since paAIP2 acts within seconds and has the same slow time course.

“The slow time course is not due to slow access of the inhibitors to the site of action, since paAIP2, a photoactivatable peptide inhibitor (203) that acts within seconds of light exposure, has the same slow time course (361).”

After transient inhibition of CaMKII with the photoactivatable inhibitor paAIP2, there is no recovery of synaptic responses.

“After the transient inhibition of CaMKII with the photoactivatable inhibitor (paAIP2) (203), there is no recovery (361).”

Numerous previous studies have failed to reverse established LTP.

“However, numerous previous studies have failed to reverse established LTP (Refs. 198, 200–203, but see Ref. 357).”

Concentrations of CaMKII inhibitors that block the induction of LTP failed to affect maintenance.

“Third, as discussed in sect. 8, concentrations of CaMKII inhibitors that block the induction of LTP failed to affect maintenance (Refs. 198, 200–203, but see Ref. 357).”