Non-canonical heterogeneous cellular distribution and co-localization of CaMKII alpha and CaMKII beta in the spinal superficial dorsal horn

作者：Larsson Max^*

来源：Brain Structure & Function, 2018, 223(3): 1437-1457.

DOI：10.1007/s00429-017-1566-0

• Pain
• Central sensitization
• Spinal cord
• Pax2
• GABA

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a key enzyme in long-term plasticity in many neurons, including in the nociceptive circuitry of the spinal dorsal horn. However, although the role of CaMKII heterooligomers in neuronal plasticity is isoform-dependent, the distribution and co-localization of CaMKII isoforms in the dorsal horn have not been comprehensively investigated. Here, quantitative immunofluorescence analysis was used to examine the distribution of the two major neuronal CaMKII isoforms, alpha and beta, in laminae I-III of the rat dorsal horn, with reference to inhibitory interneurons and neuronal populations defined by expression of parvalbumin, calretinin, and calbindin D28k. Unexpectedly, all or nearly all inhibitory and excitatory neurons showed both CaMKII alpha and CaMKII beta immunoreactivity, although at highly variable levels. Lamina III neurons showed less CaMKII alpha immunoreactivity than laminae I-II neurons. Whereas CaMKII alpha immunoreactivity was found at nearly similar levels in inhibitory and excitatory neurons, CaMKII beta generally showed considerably lower immunoreactivity in inhibitory neurons. Distinct populations of inhibitory calretinin neurons and excitatory parvalbumin neurons exhibited high CaMKII alpha-to-CaMKII beta immunoreactivity ratios. CaMKII alpha and CaMKII beta immunoreactivity showed positive correlation at GluA2(+) puncta in pepsin-treated tissue. These results suggest that, unlike the forebrain, the dorsal horn is characterized by similar expression of CaMKII alpha in excitatory and inhibitory neurons, whereas CaMKII beta is less expressed in inhibitory neurons. Moreover, CaMKII isoform expression varies considerably within and between neuronal populations defined by laminar location, calcium-binding protein expression, and transmitter phenotype, suggesting differences in CaMKII function both between and within neuronal populations in the superficial dorsal horn.

• 出版日期2018-4