Calcineurin Regulates Synaptic Plasticity and Nociceptive Transmissionat the Spinal Cord Level.
Yuying HuangShao-Rui ChenHui-Lin Pan 潘惠麟Published in: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry (2021)
Calcineurin, the predominant Ca2+/calmodulin-dependent serine/threonine protein phosphatase (also known as protein phosphatase 2B), is highly expressed in immune T cells and the nervous system, including the dorsal root ganglion and spinal cord. It controls synaptic transmission and plasticity by maintaining the appropriate phosphorylation status of many ion channels present at presynaptic and postsynaptic sites. As such, normal calcineurin activity in neurons and synapses is mainly involved in negative feedback regulation in response to increased neuronal activity and intracellular Ca2+ levels. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) are widely used as immunosuppressants in tissue and organ transplantation recipients and for treating autoimmune diseases but can cause severe pain in some patients. Furthermore, diminished calcineurin activity at the spinal cord level may play a major role in the transition from acute to chronic neuropathic pain after nerve injury. Restoring calcineurin activity at the spinal cord level produces long-lasting pain relief in animal models of neuropathic pain. In this article, we provide an overview of recent studies on the critical roles of calcineurin in regulating glutamate NMDA and AMPA receptors, voltage-gated Ca2+ channels, potassium channels, and transient receptor potential channels expressed in the spinal dorsal horn and primary sensory neurons.
Keyphrases
- neuropathic pain
- spinal cord
- protein kinase
- spinal cord injury
- end stage renal disease
- chronic kidney disease
- ejection fraction
- newly diagnosed
- liver failure
- chronic pain
- binding protein
- acute respiratory distress syndrome
- protein protein
- patient reported outcomes
- respiratory failure
- reactive oxygen species
- blood brain barrier
- cell therapy
- mesenchymal stem cells
- kidney transplantation