RT Journal Article SR Electronic T1 Spike Frequency Decoding and Autonomous Activation of Ca2+–Calmodulin-Dependent Protein Kinase II in Dorsal Root Ganglion Neurons JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6694 OP 6705 DO 10.1523/JNEUROSCI.21-17-06694.2001 VO 21 IS 17 A1 Feleke Eshete A1 R. Douglas Fields YR 2001 UL http://www.jneurosci.org/content/21/17/6694.abstract AB Autonomous activation of calcium–calmodulin kinase (CaMKII) has been proposed as a molecular mechanism for decoding Ca2+ spike frequencies resulting from action potential firing, but this has not been investigated in intact neurons. This was studied in mouse DRG neurons in culture using confocal measurements of [Ca2+]i and biochemical measurements of CaMKII autophosphorylation and autonomous activity. Using electrical stimulation at different frequencies, we find that CaMKII autonomous activity reached near maximal levels after ∼45 impulses, regardless of firing frequency (1–10 Hz), and autonomous activity declined with prolonged stimulation. Frequency-dependent activation of CaMKII was limited to spike frequencies in the range of 0.1–1 Hz, despite marked increases in [Ca2+]i at higher frequencies (1–30 Hz). The high levels of autonomous activity measured before stimulation and the relatively long duration of Ca2+ spikes induced by action potentials (∼300 msec) are consistent with the lower frequency range of action potential decoding by CaMKII. The high autonomous activity under basal conditions was associated with extracellular [Ca2+], independently from changes in [Ca2+]i, and unrelated to synaptic or spontaneous impulse activity. CaMKII autonomous activity in response to brief bursts of action potentials correlated better with the frequency of Ca2+ transients than with the concentration of [Ca2+]i. In conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz in these neurons, but other mechanisms may be required to decode higher frequencies. Alternatively, CaMKII may mediate high-frequency responses in subcellular microdomains in which the enzyme is maintained at a low level of autonomous activity or the Ca2+ transients have faster kinetics.