Expression and distribution of creatine transporter and creatine kinase (brain isoform) in developing and mature rat cochlear tissues

Abstract

Physiological processes in the cochlea associated with sound transduction and maintenance of the unique electrochemical environment are metabolically demanding. Creatine maintains ATP homeostasis by providing high-energy phosphates for ATP regeneration which is catalyzed by creatine kinase (CK). Cellular uptake of creatine requires a specific high affinity sodium- and chloride-dependent creatine transporter (CRT). This study postulates that this CRT is developmentally regulated in the rat cochlea. CRT expression was measured by quantitative real-time RT-PCR and immunohistochemistry in the postnatal (P0-P14) and adult (P22-P56) rat cochlea. The maximum CRT expression was reached at the onset of hearing (P12), and this level was maintained through to adulthood. CRT immunoreactivity was strongest in the sensory inner hair cells, supporting cells and the spiral ganglion neurons. Cochlear distribution of the CK brain isoform (CKB) was also assessed by immunohistochemistry and compared with the distribution of CRT in the developing and adult cochlea. CKB was immunolocalized in the organ of Corti supporting cells, and the lateral wall tissues involved in K(+) cycling, including stria vascularis and spiral ligament fibrocytes. Similar to CRT, CKB reached peak expression after the onset of hearing. Differential spatial and temporal expression of CRT and CK in cochlear tissues during development may reflect differential requirements for creatine-phosphocreatine buffering to replenish ATP consumed during energy-dependent metabolic processes, especially around the period when the cochlea becomes responsive to airborne sound.

Echolocation call frequency variation in horseshoe bats: molecular basis revealed by comparative transcriptomics

“…CKB, creatine kinase brain isoform, is mainly expressed in the organ of Corti supporting cells and the lateral wall tissues [64]. While not reported to be significant in the ABR test, CKB plays an essential role in replenishing ATP consumed during the process of hearing in cochlea [64], which may explain why it shows the highest expression level among all 252 DEGs identified here (average log 2 CPM of 11.28). A further DEG, SLC1A3, encodes the glutamate-aspartate transporter GLAST and is mainly expressed in the supporting cells around the inner hair cells.…”

“…Although this gene has been shown to be significant in the ABR test, it appears to relate to low hearing frequency (below 24 kHz), as is also the same case for CCDC88C, which encodes a negative regulator in the Wnt signalling pathway [63]. CKB, creatine kinase brain isoform, is mainly expressed in the organ of Corti supporting cells and the lateral wall tissues [64]. While not reported to be significant in the ABR test, CKB plays an essential role in replenishing ATP consumed during the process of hearing in cochlea [64], which may explain why it shows the highest expression level among all 252 DEGs identified here (average log 2 CPM of 11.28).…”

Mutation of the ATP-gated P2X 2 receptor leads to progressive hearing loss and increased susceptibility to noise

“…Assessments of hearing function were performed using established protocols (39). Mid-modiolar cochlear cyrosections from the quiet-chamber 17-mo old P2RX2-null and WT mice were examined by immunofluorescence confocal microscopy as described previously (40).…”

Cellular compartmentation of energy metabolism: creatine kinase microcompartments and recruitment of B-type creatine kinase to specific subcellular sites

“…BCK also has a particularly important role in sensory cells. In postnatal rat, cochlear BCK reaches peak expression at the onset of hearing (Wong et al 2012), and BCK k.o. mice show a pronounced hearing loss (Shin et al 2007).…”