title: Hypothermia reduces calcium entry via the N-methyl-D-aspartate and ryanodine receptors in cultured hippocampal neurons.
abstract: Hypothermia is a powerful neuroprotective method when induced following cardiac arrest, stroke, and traumatic brain injury. The physiological effects of hypothermia are multifaceted and therefore a better knowledge of its therapeutic targets will be central to developing innovative combination therapies to augment the protective benefits of hypothermia. Altered neuronal calcium dynamics have been implicated following stroke, status epilepticus and traumatic brain injury. This study was therefore initiated to evaluate the effect of hypothermia on various modes of calcium entry into a neuron. Here, we utilized various pharmacological agents to stimulate major routes of calcium entry in primary cultured hippocampal neurons. Fluorescent calcium indicator Fura-2AM was used to compare calcium ratio under normothermic (37 °C) and hypothermic (31 °C) conditions. The results of this study indicate that hypothermia preferentially reduces calcium entry through N-methyl-D-aspartate receptors and ryanodine receptors. Hypothermia, on the other hand, did not have a significant effect on calcium entry through the voltage-dependent calcium channels or the inositol tri-phosphate receptors. The ability of hypothermia to selectively affect both N-methyl-D-aspartate receptors and ryanodine receptors-mediated calcium systems makes it an attractive intervention for alleviating calcium elevations that are present following many neurological injuries.
authors.affiliation: Department of Neurology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298-0599, United States.
authors.forename: Kristin F
authors.initials: KF
authors.lastname: Phillips
authors.forename: Laxmikant S
authors.initials: LS
authors.lastname: Deshpande
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeLorenzo
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology*; D007036:Hypothermia, Induced; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium