Expression of phospho-Ca2+/calmodulin-dependent protein kinase II in the pre-Bötzinger complex of rats


Address correspondence and reprint requests to Dr.Ying-Ying Liu, Institute of Neurosciences, The Fourth Military Medical University, 17 Chang Le Xi Road, Xi'an 710032, China. E-mail:


The pre-Bötzinger complex (pre-BötC) in the ventrolateral medulla oblongata is a presumed kernel of respiratory rhythmogenesis. Ca2+-activated non-selective cationic current is an essential cellular mechanism for shaping inspiratory drive potentials. Ca2+/calmodulin-dependent protein kinase II (CaMKII), an ideal ‘interpreter’ of diverse Ca2+ signals, is highly expressed in neurons in mediating various physiological processes. Yet, less is known about CaMKII activity in the pre-BötC. Using neurokinin-1 receptor as a marker of the pre-BötC, we examined phospho (P)-CaMKII subcellular distribution, and found that P-CaMKII was extensively expressed in the region. P-CaMKII-ir neurons were usually oval, fusiform, or pyramidal in shape. P-CaMKII immunoreactivity was distributed within somas and dendrites, and specifically in association with the post-synaptic density. In dendrites, most synapses (93.1%) examined with P-CaMKII expression were of asymmetric type, occasionally with symmetric type (6.9%), whereas in somas, 38.1% were of symmetric type. P-CaMKII asymmetric synaptic identification implicates that CaMKII may sense and monitor Ca2+ activity, and phosphorylate post-synaptic proteins to modulate excitatory synaptic transmission, which may contribute to respiratory modulation and plasticity. In somas, CaMKII acts on both symmetric and asymmetric synapses, mediating excitatory and inhibitory synaptic transmission. P-CaMKII was also localized to the perisynaptic and extrasynaptic regions in the pre-BötC.