Compartmentation of brain-type creatine kinase and ubiquitous mitochondrial creatine kinase in neurons: evidence for a creatine phosphate energy shuttle in adult rat brain

Abstract

Multiple isoforms of creatine kinase (CK) are expressed in specific cell types as part of an energy delivery or shuttle system. To test the hypothesis that neurons utilize a creatine phosphate energy shuttle, we examined the pattern of CK isoform expression and localization in adult rat brain. Two isoforms of CK are present in brain extracts, "brain-type," or BCK, and the ubiquitous form of the mitochondrial CK (uMtCK), as detected by enzyme activity following nondenaturing electrophoresis and by Western blotting following denaturing electrophoresis. In formalin-fixed and paraffin-embedded sections of rat brain, uMtCK immunostaining is detected in the somata of all Golgi type I neurons in the cerebellum, pontine reticular formation, red nucleus, hippocampus, and cerebral cortex. Immunostaining for uMtCK appears throughout the cell body but not in nuclei. BCK immunostaining is also present in somata of Golgi type I neurons in the cerebellum, red nucleus, and pons and is distributed throughout the cell body and within nuclei. BCK immunostaining also appears in neuronal processes and is concentrated in the molecular layers of the cerebellum and the hippocampus and in cortical pyramidal cell dendrites. These results demonstrate a coordinate pattern of expression and compartmentation of BCK and uMtCK isoforms in neurons, which provides an anatomic basis for the transfer of metabolic energy via a creatine phosphate energy shuttle.