Calcium Responses To Caffeine And Muscarinic Receptor Agonists Are Altered In Traumatically Injured Neurons
Calcium imaging; Calcium stores; Cortical neurons; In vitro; Inositol (1,4,5)-trisphosphate; Intracellular free calcium; Traumatic brain injury
A fundamental mechanism that is believed to contribute to neuronal injury and death following traumatic brain injury (TBI) is a disruption in cellular calcium homeostasis. Of primary importance to these homeostatic mechanisms are intracellular calcium stores located on the endoplasmic reticulum. These intracellular stores play an important role in maintaining normal levels of calcium and calcium-mediated signaling through these stores is critical to several physiological processes in neurons. Using an in vitro model of stretch-induced traumatic injury and fura-2 digital calcium imaging, we investigated alterations in calcium-induced calcium release (CICR) and inositol (1,4,5)-trisphosphate (IP3)-linked signaling through intracellular calcium stores in populations of cultured rat cortical neurons. Caffeine, which stimulates CICR, produced a rapid elevation of intracellular free calcium ([Ca2+]i) in 70% of uninjured neurons. Fifteen min after injury the population of caffeine-responsive neurons was reduced to 30%. The IP3-linked muscarinic acetylcholine receptor agonists, CDD-0097 HCl and McN-A-343, produced elevations in [Ca2+]i in 91% and 70% of uninjured neurons, respectively. Following injury the population of responders was reduced to 19% and 26%, respectively. Differential responses to agonists were also noted after injury, in which the majority of neurons within a given culture well were unresponsive to agonists while others elicited a normal elevation of calcium. These results suggest disruptions in intracellular calcium store-mediated signaling and altered calcium signaling population dynamics following injury. These alterations could affect normal neurotransmission in the brain and may contribute to some of the pathology of TBI.
Journal of Neurotrauma
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Weber, John T.; Rzigalinski, Beverly A.; and Ellis, Earl F., "Calcium Responses To Caffeine And Muscarinic Receptor Agonists Are Altered In Traumatically Injured Neurons" (2002). Scopus Export 2000s. 2416.